This paper aims to demonstrate that, beyond the small world of Riemann-Liouville and Caputo derivatives, there is a vast and rich world with many derivatives suitable for specific problems and various theoretical frameworks to develop, corresponding to the different paths taken. Notions of time and scale sequences are introduced and general associated basic derivatives, namely right/stretching and left/shrinking, are defined. A general framework for fractional derivative definitions is reviewed and applied to get both known and new fractional order derivatives. Several fractional derivatives are considered, mainly: Liouville, Hadamard, Euler, bilinear, tempered, q-derivative, and Hahn.

Our previous in vitro reports showed that crude extract prepared with 50% ethanol (ethanol crude extract, ECE) from Mongolian oak cups possessed excellent antioxidant capacities as well as inhibitory activities against α-glucosidase, α-amylase and protein glycation caused by its enrichment in phenolics, including mainly ellagic acid, kaempferol and their derivatives. Nevertheless, few in vivo studies on antidiabetic activities of these phenolics were conducted. The present study investigated hypoglycemic effects with normal and diabetic rats being administrated orally without or with ECE at 200 and 800 mg/kg for 15 days. In normal rats, no significant differences were exhibited after ECE administration in body weight, fasting blood glucose level, levels of chelesterol, triglyceride, LDL and AST in serum, organ indexes, and levels of GSH and MDA in organs. In diabetic rats, the fasting blood glucose level, indexes of heart and liver, and levels of chelesterol and triglyceride in serum and MDA in heart tissue were significantly decreased. Moreover, HDL levels in serum and SOD activities in the four organs of diabetic rats were significantly improved after ECE administration at 800 mg/kg. Thus, in addition to inhibiting α-glucosidase, α-amylase and protein glycation reported previously, oak cups might contain novel dietary phytonutrients in preventing abnormal changes in blood glucose and lipid profile and attenuating oxidant stress in vivo. The results also implied that it is ellagic acid, kaempferol and their derivatives enriched in ECE that might play vital roles in managing type 1 as well as type 2 diabetes.

The aim of this work is research dedicated to the search for new bactericidal systems for use in cosmetic formulations, dermocosmetics, or the production of wound dressings. Over the last two decades chitosan due to its special biological activity, has become a highly indispensable biopolymer with very wide application possibilities. Literature reports on the antibacterial effects of chitosan are very diverse, but our research has shown that they can be successfully improved through chemical modification. Therefore, in this study, results on the synthesis of new Schiff bases chitosan – dCsSB-SFD and dCsSB-PCA obtained using two aldehydes: sodium 4-formylbenzene-1,3-disulfonate (SFD) and 2-pyridine carboxaldehyde (PCA) respectively. Chitosan derivatives synthesized in this way demonstrate stronger antimicrobial activity. Carrying out the procedure of grafting chitosan with a caproyl chain allowed obtaining compatible blends of chitosan derivatives with κ-carrageenan, which are stable hydrogels with a high swelling coefficient. Furthermore, covalently bounded PCL improved the solubility of obtained polymers in organic solvents. With this respect, the Schiff base-containing polymers obtained in this study, with special hydrogel and antimicrobial properties are very promising materials for the potential use as a controlled-release formulation of both, hydrophilic and hydrophobic drugs in cosmetic products for skin health.

Fractional calculus gained a lot of attention in the last couple of years. Researchers discovered that processes in various fields follow rather fractional dynamics than ordinary integer-ordered dynamics, meaning the corresponding differential equations feature non-integer valued derivatives. There are several arguments for why this is the case, one of them being that fractional derivatives’ inherit spatiotemporal memory and/or the ability to express complex naturally occurring phenomena. Another popular topic nowadays is machine learning, i.e., learning behavior and patterns from historical data. In our ever-changing world with ever-increasing amounts of data, machine learning is a powerful tool for data analysis, problem-solving, modeling, and prediction. It further provides many insights and discoveries in various scientific disciplines. As these two modern-day topics provide a lot of potential for combined approaches to describe complex dynamics, this article reviews combined approaches of fractional derivatives and machine learning from the past, puts them into context, and thus provides a list of possible combined approaches and the corresponding techniques. Note, however, that this article does not deal with neural networks, as there already is profound literature on neural networks and fractional calculus. We sorted past combined approaches from the literature into three categories, i.e., preprocessing, machine learning & fractional dynamics, and optimization. The contributions of fractional derivatives to machine learning are manifold as they provide powerful preprocessing and feature augmentation techniques, can improve physically informed machine learning, and are capable of improving hyperparameter optimization. Thus, this article serves to motivate researchers dealing with data-based problems, to be specific machine learning practitioners, to adopt new tools and enhance their existing approaches.

The general synthesis of boron-containing cyclic compounds (boracycles) necessitates toxic organotin precursors or highly reactive boron halides. Here we report the synthesis of seven- and five-membered boracycles utilizing arylboronic acid pinacol esters (ArBpins) as stable boron sources. Grignard reagents generated from 2,2′-dibromodibenzyl or 2,2′-dibromobiphenyl reacted with ArBpins, where Ar = 9-anthryl (Anth), 2,4,6-trimethylphenyl (Mes), 2,4,6-triisopropylphenyl (Tip), to give 10,11-dihydro-5H-dibenzo[b,f]borepins or dibenzoborole derivatives. This Bpin-based method was successfully applied to a one-shot double boracycle formation, providing a dihydrodibenzoborepin–anthracene–dihydrodibenzoborepin triad molecule in a good yield. The dihydrodibenzoborepin bearing the Anth group was directly converted to the unsaturated borepin by NBS/AIBN. All products were characterized by NMR, HRMS, and in some cases, single-crystal X-ray diffraction analysis. Additionally, the photophysical properties of the products are also reported.

Continuing the investigation already started (See Farcaş, A.-A.; Bende, A. PCCP 2024, 26, 14937), the light absorption and charge-transfer properties of the dopamine (DA), dopamine zwitterion (called as dopamine-semi-quinone or DsQ) and dopamine-o-quinone (DoQ) adsorbed on the graphene nanoparticle surface have been investigated using the ground state and linear-response time-dependent density functional theories, considering the B97X-D3BJ/def2-TZVPP level of theory. In terms of the strength of molecular adsorption on the surface, the DsQ form has 50 % higher binding energy than that for the DA or DoQ cases (-20.24 kcal/mol vs. -30.41 kcal/mol). The results obtained for electronically excited states and UV-Vis absorption spectra show that the photochemical behavior of DsQ is more similar to DA than that observed for DoQ. Of the three systems analyzed, the DsQ-based complex showed the most active CT phenomenon, both in terms of the number of CT-like states and the amount of charge transferred. Of the first thirty electronically excited states computed for the DsQ case, eleven are purely CT-type and nine are mixed CT and localized (or Frenkel) excitations. By varying the adsorption distance between the molecule and the surface vertically, the amount of charge transfer obtained for DA decreases significantly as the distance increases, for DoQ it remains stable, while for DsQ there are states for which little change is observed, while for others there is a significant change. Furthermore, the mechanistic compilation of the electron orbital diagrams of the individual components cannot describe in detail the nature of the excitations inside the complex.

DFT calculations on the photoisomerization reactions of pyridazine N-oxide derivatives are presented. The irradiation of 3,6-diphenylpyridazine N-oxide allowed to obtain the first excited singlet state that underwent to a ring opening reaction induced to the oxygen migration to the adjacent carbon atom, with the formation of a diazo derivative. This intermediate can give a ring closure reaction to give a pyrazole derivative, or, with a higher transition energy, it can lose nitrogen allowing the formation of 2,5-diphenylfuran. The irradiation of 3-phenylpyridazine N-oxide allowed the formation only of 2-phenylfuran. In this case, calculations allowed to explain this behavior. The first excited singlet state gave a photoisomerization reaction with the formation of the corresponding diazo intermediate. This intermediate could not be converted into the corresponding pyrazole derivative because it was converted into a N-formyl pyrazole never reported in literature. The only possible reaction is the loss of nitrogen and the formation of 2-phenylfuran.

Seeds from several Ribes taxa were surveyed for phenolic compounds and in vitro antiproliferative activity against HT-29 colorectal cancer cells. Total phenolic compounds were analysed through the Folin-Ciocalteu procedure, while phenolic profiles were analysed by LC coupled to a single mass spectrometer Orbitrap using an electrospray interface (ESI). Antitumor effects were established using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Total phenolics ranged from 11.4 in R. alpinum to 94.8 mg of caffeic acid equivalents (CAE)/g in R. nigrum 'Koksa'. Concerning phenolic compounds, four were hydroxylated benzoic acids, four cinnamic acid derivatives, eight flavonoids, and nine flavonoid glycosides. The growth inhibition against HT-29 cancer cells was exercised much better by R. nigrum 'Koksa' and Ribes 'Erkeeni' (GI50 37 and 42 µg/ml). All Ribes extracts, except R. nigrum 'Hara katarlik', showed higher activity than that of R. rubrum (GI50 at 72 h: 99 µg/ml). Interestingly, the highly bioactive extract from Ribes 'Erkeeni' contains all detected phenolics, while R. nigrum 'Koksa' lacks only populnin. Therefore, the high bioactivity found for such extracts could be due to a synergy due to all detected compounds. This work constitutes a comprehensive action for expanding knowledge on the phenolic profiles and antitumor activity of GLA-rich Ribes seeds.

Reactions of quinones with compounds containing an amino group can produce a wide variety of addition or substitution products that depend on reactivity of both quinone and amino derivative. 6,7-Dichloropyrido[1,2-a]benzimidazole-8,9-diones undergo selective nucleophilic substitution reaction with different benzohydrazides and α-hydroxy-p-quinone imine derivatives stabilized by strong intramolecular hydrogen bond were isolated. Synthesized compounds represent a combination of several structural motifs: benzimidazole core fused with α-hydroxy-p-quinone imine which contains a benzamido fragment. The protonation/deprotonation processes were investigated in a solution using UV-Vis spectroscopy and 1H NMR titration experiment. X-ray crystallography analysis revealed a set of weak non-covalent interactions such as intra- and intermolecular hydrogen bonds and π-π stacking. Additionally, the redox behavior of 6,7-dichloropyrido[1,2-a]benzimidazole-8,9-dione and its p-imino derivative was investigated in acidic and neutral environment using cyclic voltammetry measurements. Cathode material based on 6,7-dichloropyrido[1,2-a]benzimidazole-8,9-dione could act as potential effective active electrode in aqueous electrolyte batteries, however further optimization is required.

This study was designed for the first time to improve phenolic yield and antioxidant activity of ultrasonic-assisted extraction from Acer truncatum leaves (ATL) using response surface methodology, and phenolic composition in ATL extracted under the optimized condition were characterized by UPLC-QTOF-MS/MS. Solvent and extraction time were selected based on preliminary experiments, and a four-factors-three-levels central composite design was conducted to optimize solvent concentration (X₁), material-to-liquid ratio (X₂), ultrasonic temperature (X₃) and power (X₄) for an optimal total phenol yield (Y₁) and DPPH• antioxidant activity (Y₂). The results showed that the optimal combination was ethanol: water (v:v) 66.21%, material-to-liquid ratio 1:15.31 g/mL, ultrasonic temperature 60 °C, power 267.30 W, and time 30 min with three extractions, giving a maximal total phenol yield of 7593.62 mg gallic acid equivalent /100 g d.w. and a maximal DPPH• antioxidant activity of 74241.61 μmol Trolox equivalent/100 g d.w.. Furthermore, 22 phenolics were first identified in ATL extract obtained under the optimized conditions, indicating that gallates, gallotannins, quercetin, myricetin and chlorogenic acid derivatives were the main phenolic composition in ATL. What’s more, a gallotannins pathway existing in ATL from gallic acid to penta-O-galloyl-glucoside was interpreted. All these results provided practical information aiming at full utilization of phenolics in ATL, together with fundamental knowledge for further research.

We introduce a series of twisted donor-acceptor (D-A) carbazole-benzophenone based electroactive bipolar derivatives that were synthesized through the reaction of 4-fluorobenzophenone with various partially alkylated 3,3’-bicarbazoles. The comprehensive structural characterization of these compounds is provided. These amorphous materials exhibit suitable glass transition temperatures ranging from 57 to 102 °C and demonstrate high thermal stability, with decomposition temperatures reaching 400 °C. Moreover, the developed materials exhibit elevated photoluminescence quantum yields (PLQY) of up to 75.5% and favorable HOMO-LUMO levels, along with suitable triplet-singlet state energy values. Due to their good solubility and suitable film-forming properties, all the compounds were evaluated as blue emitters dispersed in 4,4’-bis(N-carbazolyl)-1,10-biphenyl (CBP) host for the fabrication of organic light-emitting diodes (OLEDs) in concentration dependent experiments. Among these experiments, the device containing 15 wt% of the guest 4-(9’-{2-ethylhexyl}-[3,3’]-bicarbazol-9-yl)benzophenone demonstrated the best characteristics, achieving maximum brightness of 3581 cd/m2, current efficiency of 5.7 cd/A, power efficiency of 4.1 lm/W and external quantum efficiency of 2.7%.

The need for solvating and encapsulating hydro-sensitive molecules drives noticeable trends in the applications of cyclodextrins in pharmaceutical industry, food, polymer, materials, and agricultural science. Among them, β-cyclodextrin is one of the most used for the entrapment of phenolic acid compounds to mask the bitterness of wheat bran. In this regard, there is still a need for a good predictive model that assesses β-cyclodextrin bitterness masking capabilities for various phenolic compounds. This study uses a dataset of 20 phenolic acids docked to the β-cyclodextrin cavity to generate three different binding constants. The data from docking study were combined with topological, topographical and quantum-chemical features from the ligands in a machine learning-based structure-activity relationship study. Three different models for each binding constant were computed using a combination of Genetic Algorithm (GA) and Multiple Linear Regression (MLR) approaches. The developed ML/QSAR models showed a very good performance, with high predictive ability and correlation coefficients of 0.969 and 0.984, for training and test sets, respectively. The models revealed several factors responsible for a binding with cyclodextrin, showing positive contributions toward the binding affinity values, including such features as presence of six-membered rings in the molecule, branching, electronegativity values, and polar surface area.

Based on DFT (density functional theory) using B3LYP/6-31G method, theoretical investigations applied to demonstrate the structural, electronic properties and stability of (N,Nˊ-(1,4-phenylene)bis(1,8-naphthalimide)) is more stable than the compound (N-(4-amino phenyl)1,8-naphthalimide) by (-1.2762 eV or -29.4299 Kcal.mol-1) depending on the values of HOMO, synthesis reaction of imide is spontaneous and endothermic at temperature 275˚C according to the values of ∆rS, ∆rG and ∆rH.

Phenolic compounds, present in plants, provide substantial health advantages, such as antioxidant and anti-inflammatory properties, which enhance cardiovascular and cognitive well-being. Australia is enriched with a wide range of plants with phytopharmacological potential, which needs to be fully elucidated. In this context, we analyzed leaves of aniseed myrtle (Syzygium anisatum), lemon myrtle (Backhousia citriodora), and cinnamon myrtle (Backhousia myrtifolia) for their complex phytochemical profile and antioxidant potential. LC-ESI-QTOF-MS/MS was applied for screening and characterizing these Australian myrtles’ phenolic compounds and the structure-function relation of phenolic compounds. This study identified 145 and quantified/semi-quantified 27 phenolic compounds in these Australian myrtles. Furthermore, phenolic contents (total phenolic content (TPC), total condensed tannins (TCT), and total flavonoids (TFC)) and antioxidant potential of phenolic extracts from the leaves of Australian myrtles were quantified. Aniseed myrtle was quantified with the highest TPC (52.49 ± 3.55 mg GAE/g) and total antioxidant potential than other selected myrtles. Catechin, epicatechin, isovitexin, cinnamic acid, and quercetin were quantified as Australian myrtles' most abundant phenolic compounds. Moreover, chemometric analysis further validated the results. This study provides a new insight into the novel potent bioactive phenolic compounds from Australian myrtles that could be potentially useful for functional, nutraceutical, and therapeutic applications.

Visible-light photocatalysis, particularly in its application to organic synthesis, has experienced a big renaissance in the past decade. The rational design of new photocatalysts with designed and improved photocatalytic properties, that at the same time circumvents the necessity of using scarce and toxic transition metals, will predictably play a key role in photocatalysis in the next few years. Although free-base porphyrins were identified some years ago as a promising, easily accessible and easily tunable class of organic photoredox catalysts, a systematic study on the effect of the electronic nature and of the position of the substituents on both the ground-state and the excited-state redox potentials of these compounds is still lacking. We have prepared a set of known functionalized derivatives of meso-tetraphenyl porphyrin containing different substituents either in one of the meso-positions or at a beta-pyrrole carbon and we have determined their ground- and (singlet) excited-state redox potentials. This survey has led us to conclude that the introduction of a carbonyl group at the beta-pyrrolic position strongly increases the facility of the monoelectronic reduction of the porphyrin both in the ground state and in the singlet excited state. We have also prepared a second set of four previously unknown benzoyl derivatives of meso-tetraphenylporphyrin, and we have confirmed the validity of our conclusions.

Chagas disease (CD) is a neglected tropical parasitic disease caused by the protozoan Trypanosoma cruzi. Unfortunately, the current etiological treatment for CD is unsatisfactory, due to the high toxicity and low cure efficacy of compounds, mainly during the chronic phase of this disease. Thus, the discovery of new drugs for the treatment of CD is urgent. In the present study, we report the synthesis of a series of guanidines and its evaluation in in vitro assays to determine the trypanocidal effects on the Tulahuen T. cruzi strain, transfected with a β-galactosidase reporter gene, in comparison to the cytotoxic effects on vertebrate cells. The most potent and selective compounds LQOF-G1 and LQOF-G29 were considered good drug prototypes and candidates for in vivo tests using mice. Both compounds possess an electron withdrawing group on the aniline moiety, namely a NO2 and Br group, respectively, which effectively decrease the electron density. LQOF-G29 stands out among the investigated compounds due to the replacement of the benzyl group by methyladamantane.

Pluripotent stem cells (PSCs) hold many potential research and clinical benefits due to their ability to differentiate into nearly every cell type in the body. They are often used as model systems for early stages of ontogenesis to better understand key developmental pathways, and for drug screening. However, in order to fully realise the potential of PSCs and their translational applications, a deeper understanding of developmental pathways, especially in humans, is required. Several signalling molecules play important roles during development and are required for proper differentiation of PSCs. The concentration and timing of signal activation is important, with perturbations resulting in improper development and/or pathology. Bone morphogenetic protein (BMP) is one such key signalling molecule involved in the specification and differentiation of various cell types and tissues in the human body including tooth and otic development. In this review, we describe the role of BMP signalling and its regulation, the consequences of BMP dysregulation in disease and differentiation, and how PSCs can be used to investigate the effects of BMP modulation during development, mainly focusing on otic development. Finally, we emphasise the unique role of BMP4 in otic specification and how refined knowledge in controlling its regulation could lead to the generation of more robust and reproducible human PSC-derived otic organoids for research and translational applications.

Herbal Coffee is getting more popular due to its unique flavor and higher concentration of bioactive compounds, mainly polyphenols. Rosemary is a unique herb with potent antioxidant properties. A green technique called ultrasound aids in releasing bioactive substances from the plant cell wall. In this context, ultrasound-assisted herbal coffee prepared and their anti-diabetic, anti-Alzheimer, and antioxidant activities were measured while the LC/MS was used to determine the bioactive components from the herbal coffee infusion. A total of 95 secondary metabolites were putatively reported, including alkaloids, phenolic acids, and flavonoids, which we identified in the herbal coffee infusion. The total phenolic content (61.5 ± 5.1 mg GAE/g), total flavonoid content (19.3 ± 0.9 mg QE/g), and total condensed tannin (7.6 ± 0.7 mg CE/g) of herbal coffee infusion were observed to be highest of the two remaining samples. The herbal coffee extracts were used to determine all samples' antioxidant, anti-diabetic, and anti-Alzheimer activities. Using LC-MS/MS, we semi-quantified 19 phenolic metabolites. The results show numerous bioactive components in herbal coffee infusion with more potent antioxidant, antidiabetic, and anti-Alzheimer potential. Moreover, more studies must be conducted to confirm how the metabolomic profile of herbal coffee affects its flavor profile.

The Paeonia suffruticosa, called as 'Feng Dan', has been used for thousands of years in traditional Chinese medicine. In our chemical investigation on the root bark of the plant, five new phenolic dimers, namely paeobenzofuranone A‒E (1‒5), have been characterized. Their structures were determined by spectroscopic analysis including 1D and 2D NMR, HRESIMS, UV, and IR, as well as ECD calculations. Compounds 2, 4, and 5 showed cytotoxicity against three human cancer cell lines with IC50 values ranging from 6.7 to 25.1 μM. Compounds 1 and 2 showed certain inhibitory activity on NO production. To the best of our knowledge, the benzofuranone dimers and their cytotoxicity of P. suffruticosa are reported for the first time.

Almost fifty years after the introduction of antibiotics as an antimicrobial agent, we are facing an increasing number of multi-resistant microbials. The search for new antimicrobial compounds emerged as a promising alternative to treatments for diseases caused by microorganisms such as fungi and bacteria. Thus, endophytic fungi are gaining recognition for their varied metabolites that may possess antimicrobial properties. In our research, we isolated, from Calea pinnatifida, six endophytic fungi identified as Colletotrichum siamense, Colletotrichum karstii, Hypomontagnella barbarensis, Neopestalotiopsis clavispora, Nigrospora sacchari-officinarum and Annulohypoxylon moriforme. Analyses of microbial secondary metabolites by utilizing UHPLC-HR-ESI-MS/MS in conjunction with molecular networking, allowed the annotation of 9 compounds, 5 of them from GNPS spectral library match, and 4 from prediction-based on the molecular network, and allowed the isolation of two pairs of Acyl-tetronic acid derivatives distereoisomeric identified by NMR spectrum. In this sense, the present study underlines the value of endophytic fungi as a reservoir of potentially new antimicrobial agents.

Microgreens (young, edible plantlets) are a remarkable opportunity for both consumers, to benefit from health promoting compounds and for applied research, as such organisms have a very high plasticity related to environmental cues, allowing biotechnology development with low costs. Ocimum basilicum species naturally synthesize valuable, phenolic compounds, among which rosmarinic acid is most prominent. Basil plantlets were grown for 10 days under either full spectrum light (white light) or modulated blue:red:far-red:UV spectrum with an additional factorization, by applying fertilisation. Biomass accumulation reached up to 0.8 g/20 plantlets, while chlorophyll fluorescence was in the 0.75 – 0.78 range and remained uniform across treatments, indicating that no significant stress was exerted under modified light treatment. However, total phenolic contents and, in particular, rosmarinic acid contents were markedly enhanced (up to 7.5 mg/g in the red cultivar) under modulated light treatment and fertilization, compared to full spectrum light. Moreover, gene expression was enhanced, 1.3-6.3 fold for genes coding for enzymes involved in phenylpropanoid synthesis patwhays, such as phenylalanine ammonia lyase (PAL), Catechol-O-methyltransferase (COMT) and renin-angiotensin system (RAS). Overall, light modulation coupled with fertilization led to the production of basil microgreens with up to 10% more total phenolics and up to 25% more rosmarinic acid.

Many medicinal plants and their essential oils are used to treat or prevent diseases without the risk of mutagenicity, carcinogenicity, or teratogenicity. Eucalyptus essential oils are commonly used as preservatives, flavoring agents, and in various consumer goods. Eucalyptus leaves are being widely studied due to their volatile essential oils, including 1,8-cineole, p-cymene, α and β-pinene, limonene, citronellal, citral, eudesmol, terpinen-4-ol, terpineol, α–phellanderene, and 9β-sitosterol. Among these compounds, 1,8-cineole is the most abundant. Eucalyptus leaves are rich in flavonoids and phenolic compounds and are thus a great source of antioxidants. 2,2-diphenyl-1-picrylhydrazyl (DPPH), Ferric Reducing Antioxidant Power (FRAP), and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays are used to measure antioxidant capacity. The antioxidant activity of Eucalyptus essential oil is stronger than that of standard antibiotics like Erythromycin, Cefixime, and Gentamicin due to the presence of significant terpenoids in addition to phenolic chemicals and flavonoids. The lower the IC₅₀ value, the higher the antioxidant potential. Phenolic compounds and flavonoids are often associated with beneficial health outcomes, including anti-inflammatory and antioxidant effects, anti-cancer properties, reduced risk of cardiovascular diseases, prevention of age-related neurodegenerative diseases, and prevention of Alzheimer’s disease. Flavonoids also play an essential role in plants, including protecting against reduction, fertility, reproduction, and infection. Due to their anti-inflammatory, anti-oxidative, and immune-modulatory properties, flavonoids are crucial for pharmacological, medical, and nutraceutical applications.

Nano-titanium has excellent corrosion resistance and can be widely used in the field of corrosion resistant coatings. This paper introduces nano-weight titanium modified phenolic resin coatings and their anti-corrosion properties to explore the principle of nano-titanium modification and the mechanism of anti-corrosion to further develop more advanced corrosion resistant coatings. The article uses scanning electron microscopy, Fourier transform infrared spectroscopy, Raman spectroscopy and UV-Vis spectrophotometer to characterise the morphology and structure of the nano-titanium modified phenolic resin coatings and to determine the corrosion resistance properties of the modified phenolic resin coatings. The results show that the 4% nano-titanium modified phenolic resin coating, nano-titanium powder and phenolic resin will maximize the dispersion and combination, and the structure is good; nano-titanium grafted on phenolic resin, the successful preparation of nano-titanium modified phenolic resin; modified nano-titanium added to improve the coating's ability of UV absorption. The corrosion resistance of the coating is much better than that of the unmodified phenolic resin coating.

Skin cancer is a condition characterized by the abnormal growth of skin cells, primarily caused by exposure to ultraviolet (UV) radiation from the sun or artificial sources like tanning beds. Different types of skin cancer include melanoma, basal cell carcinoma, and squamous cell carcinoma. Despite the advancements in targeted therapies, there is still a need for a safer, highly efficient approach to preventing and treating cutaneous malignancies. Spices have a rich history dating back thousands of years and are renowned for their ability to enhance the flavor, taste, and color of food. Derived from various plant parts like seeds, fruits, bark, roots, or flowers, spices are important culinary ingredients. However, their value extends beyond the culinary realm. Some spices contain bioactive compounds, including phenolic compounds, which are known for their significant biological effects. These compounds have attracted attention in scientific research due to their potential health benefits, including their possible role in disease prevention and treatment, such as cancer. This review focuses on examining the potential of spice-derived phenolic compounds as preventive or therapeutic agents for managing skin cancers. By compiling and analyzing the available knowledge, this review aims to provide insights that can guide future research in identifying new anticancer phytochemicals and uncovering additional mechanisms for combating skin cancer.

Cherries have been largely investigated due to their high content in phenolics in order to fully ex-plore their health-promoting properties. Therefore, this work aimed to assess, for the first time, the anti-inflammatory potential of phenolic-targeted fractions of Saco cherry, using RAW 264.7 mac-rophages stimulated with lipopolysaccharide. Additionally, the cytotoxic effects on gastric ade-nocarcinoma (AGS), neuroblastoma (SH-SY5Y) and normal human dermal fibroblast (NHDF) cells were evaluated, as well as the ability to protect these cellular models against induced oxidative stress. The obtained data revealed that cherry fractions can interfere with cellular nitric oxide (NO) levels by capturing NO radicals and decreasing inducible nitric oxide synthase and cyclooxygen-ase-2 expression. Furthermore, it was observed that all cherry fractions exhibited dose-dependent cytotoxicity against AGS cells, presenting cytotoxic selectivity for these cancer cells when compared to SH-SY5Y and NHDF cells. Regarding their capacity to protect cancer cells against oxidative injury, in most assays, the total cherry extract was the most effective. Overall, this study reinforces the sweet cherries incorporation in new pharmaceutical products, smart foods and nutraceuticals.

Glycerol conversion to valuable biomolecules has been a research avenue that has attracted a significant interest in recent years due to its increasing over production, with possibilities for chemical transformation for eco-friendly processes and distinct compounds with biological activities. Also, in the current climate change in which a major emphasis is being placed on the design of green processes, solvents are key factors from both an economic and environmental point of view. In this context, due to its abundance and low-price, glycerol represents an innovative solvent coming from biomass and produce in high amount. On the other hand, Epichlorydrin, Glycidol and Solketal have become useful intermediates in chemical transformations when using glycerol as a raw material. This review focuses on glycerol as a green solvent in the synthesis of complex molecules, Epichlorydrin, Glycidol, Solketal and Tosyl solketal as an efficient recycling process for glycerol, as well as building blocks in the synthesis of glycerol derivatives, which are undeniable new source of potentials drugs.

The bilateral tempered fractional derivatives are introduced generalising previous works on the one-sided tempered fractional derivatives and the two-sided fractional derivatives. An analysis of the tempered Riesz potential is done and showed that it cannot be considered as a derivative.

5-(4-aminophenyl )-2-amino -1,3,4-thiadiazole was prepared by reaction of Thiosemicarbazide with 4-amino benzoic acid under reflux condition for 7 hours. The compound which has been synthesized successfully was subjected to addition reaction with 4-(Dimethylamino) benzaldehyde under reflux condition for 6 hours to synthesize Schiff bases. These compounds was characterized by using FTIR) and evaluated for their anticancer activity. The effect of (1, 3, 4-thiadiazole derivative) on the activity of malignant cells was studied by using different types of cell lines [Breast cancer, and human prostate cancer]. And was used the Electron microscope to show that the effect of the derivative on the cancer cells before and after 3 days of the injection time. It was found that the Schiff base of thiadiazole-1,3,4-(Dimethylamino)benzylidineamino]- [4-2-phenyl]amino was effective in reducing the size and density of malignant cells. That of 46.7 while in breast ) 145(DUprostate for growth inhibition produce of equal 85.9 µg/ml.

The potentiality of cv. Malbec grape pomace (GP) as a functional ingredient in the formulation of bakery foods (muffins, biscuits and cereal bars) was studied. The effect of GP addition on the phenolic compounds (PCs) composition, nutritional and sensory properties were evaluated. The addition of GP increased the content of dietary fiber, proteins, ash, total phenolic content (TPC), antioxidant activity (AA), anthocyanins and non-anthocyanins PCs while decreasing the carbohydrates content. The main PCs given by the GP to supplemented foods were (-)-gallocatechin, quercetin-3-O-glucoside, rutin, caffeic acid, syringic acid and (+)-catechin. For anthocyanins, the acylated derivatives were more stable to heat treatment (baking) in food processing which was evidenced by a higher proportion of these PCs compounds when compared to the same derivatives quantified in GP. In general, when the TPC or individual concentrations of PCs were analyzed in a nutritional or functional context, one portion of the supplemented foods showed levels high enough to satisfy the recommended dose per day of these bioactive compounds. Additionally, the foods were well received by consumers during the sensory evaluation and supplemented biscuits got the highest acceptability. This study demonstrated that GP could be a viable functional ingredient in bakery foods to give nutritionally enhanced properties like TPC, PCs, AA and dietary fiber in consumer’s diets.

The main purpose of our research is the evaluation of the efficacity of solvent polarity on phenolic composition, as well as the antibacterial, and antioxidant activities of extract of Moroccan Mentha aquatica L., leaves. To attempt these objectives, the HPLC-DAD was used to identify the biomolecules. The total amount of phenolic and flavonoid content was determined using the Folin-Ciocalteu and aluminum trichloride processes as well as the DPPH, RP, and TAC tests were used to evaluate the antioxidant capabilities. In addition, by employing both in vitro and in silico analysis through the microdilution method, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the extracts were assessed against multidrug-resistant bacteria. Furthermore, the High-Performance Liquid Chromatography (HPLC) analysis indicated that all extracts of M. aquatica were abundant in noteworthy phytochemical compounds, especially gallic acid, vanillic acid, chlorobenzoic acid, quercetin, and kaempferol. Furthermore, the results indicated that the total phenolic content was higher in hydroethanolic extract (62.19 ± 1.19 mg GAE/g DW) in contrast to the acetonic and aqueous extracts (22.22 ± 0.64, and 22.44± 0.57 mg GAE/g DW) respectively. Similarly, the aqueous ethanol extract contained the greatest flavonoid concentration, with values of 29.15± 0.09 mg QE/g DW when compared with the other extracts. The seam extract poses excellent antioxidant power with an IC50 of 0.06 ± 0.00 mg/mL for the DPPH test, and lower RP with EC50 of 80± 0.00 µg/ml when compared with acetonic and aqueous extract (370± 0.00 and 460± 0.01 µg/mL) respectively. Moreover, the hydroethanolic extract has a high level of TAC 75.09± 2.00 mg EAA/g DW, followed by aqueous extract carrying a value of 28.53 ± 1.36 mg EAA/g DW. The antibacterial capacity is ranged between 0.78 ± 0.05 mg/mL and 12.60 ± 0.00 mg/L. The results of the in-silico study demonstrated that quercetin, vanillic acid, and naringenin components contribute to the antioxidant capability. While gallic acid, kaempferol, and quercetin components are attributed to the antibacterial capacity.

Biomaterials have been the subject of extensive research, with their applications in medicine and pharmacy expanding rapidly. Collagen and its derivatives stand out as valuable biomaterials due to their high biocompatibility, biodegradability, and lack of toxicity and immunogenicity. This review comprehensively examines collagen from various sources, its extraction and processing methods, and its structural and functional properties. Preserving the native state of collagen is crucial for maintaining its beneficial characteristics. The challenges associated with chemically modifying collagen to tailor its properties for specific clinical needs are also addressed. The review discusses various collagen-based biomaterials, including solutions, hydrogels, powders, sponges, scaffolds, and thin films. These materials have broad applications in regenerative medicine, tissue engineering, drug delivery, and wound healing. Additionally, the review highlights current research trends related to collagen and its derivatives. These trends may significantly influence future developments, such as using collagen-based bioinks for 3D bioprinting or exploring new collagen nanoparticle preparation methods and drug delivery systems.

This paper investigates pseudo-polymorphism in 2-pyridylmethoxy derivatives of p-tert-butylcalix[4]arene (PyC4), p-tert-butyldihomooxa-calix[4]arenes (PyHOC4), and p-tert-butylhexahomotrioxacalix[3]arenes (PyHO3C3), presenting 11 crystal structures with 15 crystallographically independent molecules. The macrocycle of PyC4 is smaller and less flexible with respect to those of PyHOC4 and PyHO3C3 and in solution, the cone conformation of these three molecules exhibit different point symmetries: C4, Cs and C3, respectively. A correlation is observed between the macrocycle's structural rigidity and the number of pseudo-polymorphs formed. The more rigid PyC4 displays a higher number (6) of pseudo-polymorphs compared to PyHOC4 and PyHO3C3, which exhibit a smaller number of crystalline forms (3 and 2, respectively). The X-ray structures obtained show that the conformation of the macrorings is primarily influenced by the presence of an acetonitrile guest molecule within the cavity, with limited impact from crystal packing and intermolecular cocrystallized solvent molecules. Notably, both calix[4]arene derivatives produce host-guest complex with acetonitrile, while the most flexible and less aromatic PyHO3C3 do not give crystals with acetonitrile as guest. Intertwined 1D and 2D solvent channel networks were observed in the PyHOC4-hexane and in the PyHO3C3-H2O-MeOH crystal structures, respectively, while the other pseudopolymorphs of PyHOC4 and PyHO3C3 and all PyC4 crystal forms exhibit a closely packed crystal structures without open channels.

Diarrhea remains one of the leading causes of mortality worldwide, especially among children. Recent epidemiological studies conducted in developing countries identified Shigella species as the most predominant pathogenic bacteria responsible for diarrhea. Antimicrobial therapy is necessary for Shigella infections; however, the rapid emergence of resistance against existing antimicrobials in Shigella spp. poses a serious global health problem. To identify alternative antimicrobial compounds with activity against Shigella species, the pathogens responsible for bacterial diarrhea. In this study, we have applied antibacterial phenotypic screening to identify potent anti-Shigella compounds across a broad chemical diversity, including selected acetaminophen derivatives containing benzothiazoles backbone, and their combination with certain antibiotics. In continuation to our effort in searching potent antimicrobial compounds, we have found this time around that two acetaminophen derivatives containing benzothiazoles backbone (4a and 4b) could inhibit the growth of Shigella flexneri with common MIC value of 12.5 µg/ml. These compounds were established through a time-kill kinetics’ study to be bactericidal. Meanwhile, the 2-aminobenzothiazoles (1a and 1b) used for the synthesis of compounds 4 (a & b) were found to be poorly active (MIC: 100 µg/ml) against this pathogen. Combination studies of 4a and 4b with the least susceptible antibiotics (ceftriaxone and cotrimoxazole) demonstrated synergistic anti-Shigella activity. The present study demonstrates that the azobenzothiazole dyes 4 (a & b) can be repurposed as potential anti-Shigella compounds, which can serve as scaffolds for the development of new agents against infectious diarrhea caused by Shigella and other enteric pathogens, especially in developing countries.

Xanthone derivatives, a class of natural compounds abundantly found in plants such as mangosteen (Garcinia mangostana) and certain herbs, have garnered substantial interest due to their diverse pharmacological properties, including antioxidant, anti-inflammatory, and anti-cancer activities. Recent investigations have unveiled their potential as modulators of enzymatic activity, prompting exploration into their effects on hyaluronidase-mediated HA degradation, and their effects in topical treatment of telangiectasia and rosacea. Telangiectasia and rosacea are common dermatological conditions characterized by chronic skin inflammation, vascular abnormalities, and visible blood vessels, resulting in significant cosmetic concerns and impaired quality of life for affected individuals. This review aims to provide a comprehensive overview of the current understanding regarding the interplay between mechanisms of action by which xanthone derivatives exert their therapeutic effects, including the inhibition of pro-inflammatory cytokines, modulation of oxidative stress pathways, and regulation of vascular endothelial growth factors. Furthermore, we will discuss the implications of harnessing xanthone derivatives as therapeutic agents for mitigating vascular dysfunction and its associated pathologies, thereby offering insights into future research directions and therapeutic strategies in the field of vascular biology.

Cordycepin has good antitumor activity, but its clinical application is limited due to the easy deamination of N6 in structure. In this study, a large lipopolysis group was introduced at the cordycepin N6 to improve the problem, Cordycepin derivatives(3a-4c) were synthesized, and biological evaluation of compounds were studied. In the study, the vitro antitumor activity of the compounds against MCF7 cells, HepG2 cells and SGC-7901 cells was evaluated by MTT assay. In the results, compound 4a showed the most obvious inhibitory effect on MCF7 cells with IC50 value of 27.566±0.52 μM, which was much lower than cordycepin. Compound 4a showed high selectivity between MCF7 and normal MCF-10A cells. Further biological evaluation showed that compound 4a promoted apoptosis and blocked the cell cycle in G0/G1 phase. Then, Western Blot was used to detect related apoptotic proteins. It was found that Compound 4a could down-regulate the expression of Bcl-2 protein and up-regulate the expression of p53, Bax, Caspase-3, and Caspase-9 proteins. The mitochondrial membrane potential decreased continuously and the positive expression rate decreased. It was speculated that compound 4a induced the apoptosis of MCF7 cells through the mitochondrial pathway.

High-density olive groves, despite their interesting production potential, have several limitations, also due to the high fruit load and the irrigation requirements.The study aimed to evaluate the effects of fruit load and deficit irrigation on oil yield and fruit quality, and on olive chemical composition in a high-density olive grove (cv Sikitita). Our main hypothesis was that the primary metabolism, as influenced by crop load and stress, could modify the accumulation of different phenolic classes.Different fruit loads were generated through flower thinning (66%, 50%, 33%, 0%) and two deficit irrigation treatments (-60%, -75%) were compared to the well-watered control (920 m3/ha).Thinning treatments had a limited effect on oil yield, on the other hand, deficit irrigation caused considerably less oil accumulation in the fruit on all sampling dates.Thinning 66% and deficit irrigation 75% were considered with the control for untargeted metabolomic analysis, considering three sampling dates. 233 different phenolic compounds were annotated. Multivariate HCA results indicated the impact of harvest time on the phenolic profile of olive fruits, yielding two separate clusters grouping t1 and t2 together and apart from t3. Regarding agronomic techniques, they played a differential role in the phenolic profile (supervised OPLS – DA). Fruit load mostly affected flavonoid glycosides. In contrast, the phenolic response to deficit irrigation is more heterogeneous, with phenolic acids (35%), flavonoids (25%), LMW, and other phenols (25%).

Cardiovascular diseases (CVDs) a leading cause of mortality worldwide. Therefore, there is in-creasing interest in dietary interventions to reduce risk factors associated with these conditions. Cherries and berries are rich sources of bioactive compounds and have attracted attention for their potential cardiovascular benefits. This review summarizes the current research on the effects of cherries and berries consumption on cardiovascular health, including in vivo studies and clinical trials. These red fruits are rich in phenolic compounds, such as anthocyanins and flavonoids, which have multiple bioactive properties. These properties include antioxidant, anti-inflammatory, and vasodilatory effects. Studies suggest that regular consumption of these fruits may reducing in-flammation and oxidative stress, leading to lower blood pressure, improved lipid profiles, and enhanced endothelial function. However, interpreting findings and establishing optimal dosages is challenge due to the variability in fruit composition, processing methods, and study design. Despite these limitations, the evidence highlights the potential of cherries and berries as components of preventive strategies against CVD. Further research is needed to maximize their health benefits and improve clinical practice.

In globe artichoke both the edible portion and the waste biomass are recognized as valuable sources of bioactive compounds. For this study, heads with 30 cm-long floral stems, including 2-3 leaves, were harvested from five genotypes which included two traditional vegetatively-propagated varietal types (‘Brindisino,’ and ‘Violetto di Foggia,’) and three "seed"-propagated hybrids (‘Tempo,’ ‘Opal,’ and ‘Madrigal’). The study aimed to determine the total and individual polyphenolic concentrations (measured spectrophotometrically and by HPLC) and antioxidant activity (AA) in different artichoke parts, namely the "hearts" (H), head waste (HW), stem waste (SW), and leaf waste (LW). ‘Brindisino’ SW exhibited the highest accumulation of luteolin (26,317 mg kg−1 F.W.), while ‘Tempo’ H displayed the highest cynarin content (190 mg kg−1 F.W.). ‘Tempo’ HW and H showed the highest levels of apigenin (640 mg kg−1 F.W.), and the greatest source of chlorogenic acid was found in the HW of ‘Opal’ and the H of ‘Brindisino’ (4,300 mg kg−1 F.W.). The hybrids generally exhibited lower total polyphenolic concentrations than the traditional genotypes, particularly evident in the LW. The SW demonstrated the highest concentration of total polyphenols (18,000 mg kg−1 F.W.), followed by the edible H and non-edible HW (12,000 mg kg−1 F.W.), while the LW exhibited the lowest concentration (2,000 mg kg−1 F.W.). Interestingly, the AA did not precisely align with the total polyphenolic concentration, showing slight variations between the examined parts and genotypes.

There is a great interest in finding antioxidants and products with antimicrobial activities from natural sources. The aim of this study was to obtain and identify the phenolic components and organic acids from Camellia oleifera cake. In addition, their antioxidant and antimicrobial activities were also investigated. The purity of phenolic components and organic acids obtained were 94.1 ± 0.5% w/w and 96.0 ± 0.3% w/w, respectively. There are 15 phenolic components have been detected and identified by HPLC-ESI-MS. Oxalic, citric, acetic, malic, and succinic acids are found to be major organic acids. The phenolic components and organic acids both had good antioxidant capacity, evaluated by 4 antioxidant activity assays (hydroxyl radical scavenging, superoxide radical scavenging, 1,1-diphenyl-2-picryl-hydrazyl radical scavenging and lipid peroxidation inhibition). In addition, the phenolic components and organic acids exhibited significant inhibitory activity against bacteria Staphylococcus aureus, Escherichia coli, Bacillus subtilis, and fungi Mucor racemosus, Aspergillus oryzae, Rhizopus stolonifer. The phenolic components and organic acids from C. oleifera cake both showed good antioxidant capacity and exhibited antimicrobial activities. These results may be useful for the future use of phenolic components and organic acids from C. oleifera cake.

Background: The identification of novel therapeutic strategies for Ovarian cancer (OC), the most lethal gynecological neoplasm, is of utmost urgency. Here, we have tested the effectiveness of the compound 2c (4-Hydroxy-2,6-bis(4-nitrobenzylidene)cyclohexanone 2). 2c interferes with cyste-ine-dependent deubiquitinating enzymes (DUBs), thus affecting the ubiquitin-proteasome de-pendent degradation of proteins. Methods: 2c phenotypic/molecular effects were studied in two OC cell lines, primary tumor cells cultured in 2D/3D and in a mouse xenograft model. We also propose an in-silico model of 2c interaction with DUBs. Finally, we tested the effect of 2c conju-gated to several linkers to generate 2c-derivatives usable for improved drug delivery. Results: 2c effectively impairs OC cell line and primary tumor cell viability in both 2D and 3D conditions. The effectiveness is confirmed in a xenograft mouse model of OC. We show that 2c impairs pro-teasome activity and triggers apoptosis most likely by interacting with DUBs; we propose a mechanism for the interaction with a model DUB via an in-silico evaluation of the en-zyme-inhibitor complex. 2c also reduces cell growth by down-regulating the level of the transcrip-tion factor E2F1. Finally, 2c activity is often retained after the conjugation with linkers. Conclu-sion: Our data strongly support the potential therapeutic value of 2c/derivatives in OC.

In this present study, 3-pentadecyl-phenol was selected as a modifier to prepare a foamable phenolic resin with excellent performance, which was successfully prepared by in-situ modification. Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance (¹H NMR, ¹³C-NMR) were used to test and characterize the molecular structure of the modified resin. The results showed that 3-pentadecyl-phenol successfully modified the molecular structure of phenolic resin with a reduction in resin gel time. The effect of changing the added amount of 3-pentadecyl-phenol on the mechanical properties, microstructure and flame retardancy of the modified foam was investigated. The results showed that when the amount of added 3-pentadecyl-phenol was 15% of the total amount of phenol, this resulted in the best toughness of the modified foam, which could be increased to 300% compared to the bending deflection of the unmodified phenolic foam. The cell structure showed that the modified phenolic foam formed a more regular and dense network structure and the closed cell ratio was high. Furthermore, the compressive strength, bending strength, and limited oxygen index were improved, while the water absorption rate was lowered. However, the foam density could be kept below 40 mg/cm³, which does not affect the load.

Indole is a versatile pharmacophore widely distributed in bioactive natural products. This privileged scaffold has been found in a variety of molecules isolated from marine organisms such as algae and sponges. Among these, indole alkaloids represent one of the biggest, most promising family of compounds, having shown a wide range of pharmacological properties, including anti-inflammatory, antiviral and anticancer activities. The aim of this review is to show the current scenario of marine indole alkaloid derivatives, covering not only the most common chemical structures, but also new synthetic routes developed during the last years as well as promising therapeutic applications.

Phenolic compounds represent a group of secondary metabolites that serve essential functions in plants. Beyond their positive impact on plant, these phenolic metabolites, often referred to as polyphenols, possess a range of biological properties that can promote skin health. Scientific research indicates that using phenolics derived from plants topically can be advantageous, but the activity and stability highly depend on storage of the source material and the extract method. These compounds have the ability to relieve symptoms and hinder the progression of different skin diseases. Because they come from natural sources and have minimal toxicity, phenolic compounds show potential in addressing the causes and effects of skin aging, skin diseases, and various types of skin damage, such as wounds and burns. Hence, this review provides an extensive information of the particular crops from which by-product phenolic compounds can be sourced, but pointing the need investigation according to a proper storage plant material and the choice of the best extracting method, along with an examination of their specific functions and the mechanisms by which they act to protect skin.

Silybin is a natural compound extensively studied for its hepatoprotective, neuroprotective and anti-cancer properties. Envisioning the enhancement of silybin potential by suitable modifications in its chemical structure, here, a series of new 7-O alkyl silybins derivatives were synthesized by Mitsunobu reaction starting from the silybins and tyrosol-based phenols, such as tyrosol (TYR, 3), 3-methoxytyrosol (MTYR, 4) and 3-hydroxytyrosol (HTYR, 5). This research sought to explore the antioxidant and anticancer properties of new eighteen derivatives and their mechanisms. In particular, the antioxidant properties of new derivatives outlined by DPPH assay, showed a very pronounced activity depending on the tyrosyl moiety (HTYR>MTYR>>TYR). A significant contribution of the HTYR moiety was observed for silybins and 2,3-dehydro-silybin based derivatives. According to the very potent antioxidant activity, 2,3-dehydro-silybin derivatives 15ab, 15a and 15b exerted the most potent anticancer activity in human prostate cancer PC-3 cells. Furthermore, flow cytometric analysis for cell cycle and apoptosis revealed that 15ab, 15a and 15b induce strong G1 phase arrest and increase late apoptotic population in PC-3 cells. Additionally, western blotting for apoptotic marker cleaved caspase-3 confirmed apoptosis induction by these silybin derivatives in PC-3 cells. These findings hold significant importance in the investigation of anticancer properties of silybin derivatives and strongly encourage swift investigation in pre-clinical models and clinical trials.

β-Lactams are pharmacologically important compounds because of their various biological uses, including antibiotic and so on. β-Lactams were synthesized from benzylidene-inden derivatives and acetoxyacetyl chloride. The inhibitory effect of these compounds was also examined for human carbonic anhydrase I and II (hCA I, and II) and acetylcholinesterase (AChE). The results reveal that β-lactams are inhibitors of hCA I, II and AChE. The K_i values of β-lactams (2a-k) were 0.44-6.29 nM against hCA I, 0.93-8.34 nM against hCA II, and 0.25-1.13 nM against AChE. Our findings indicate that β-lactams (2a-k) inhibit both CA isoenzymes and AChE at low nanomolar concentrations.

Fibrosis is a ubiquitous pathology, and prior studies have indicated that various artemisinin (ART) derivatives (including artesunate (AS), artemether (AM), and dihydroartemisinin (DHA)) can reduce fibrosis in vitro and in vivo. The medicinal plant, Artemisia annua L., is the natural source of ART and is widely used, especially in underdeveloped countries, to treat a variety of diseases including malaria, while A. afra contains no ART but is also antimalarial. Using human dermal fibroblasts (CRL-2097), we compared the effects of A. annua and A. afra tea infusions, ART, AS, AM, DHA, and a liver metabolite of ART, deoxyART (dART), on fibroblast viability and expression of key fibrotic marker genes after 1 and 4 days of treatment. AS, DHA, and Artemisia tea significantly reduced fibroblast viability at 1 and 4 d post-treatment. After 4 d post treatment, AS, DHA, and A. afra tea downregulated ACTA2, and upregulated MMP3, with other genes either being unaffected or differentially affected. ART and AM had no significant effect on either fibroblast viability or fibrotic gene expression. Although A. annua contains ART, it had a significantly greater anti-fibrotic effect than ART alone. Immunofluorescent staining for smooth muscle α-actin (α-SMA) correlated well with transcriptional responses of drug-treated fibroblasts. Together, proliferation, qPCR, and immunofluorescence results show that treatment with ART, AS, DHA, and the two Artemisia teas yield differing responses, including those related to fibrosis, in human dermal fibroblasts.

The goal of this study is to synthesize, determine the structure, and examine the antimicrobial properties of novel metal complexes of 2,4-dithiouracil and its derivatives. These complexes were obtained by mixing aqueous solutions of the corresponding metal salts with the ligand dissolved in DMSO and aqueous NaOH, using a metal-to-ligand ratio of 1:4:2. The structures of the new compounds were analyzed by melting point determination, microwave plasma atomic emission spectrometry (MP-AES) for Cu and Au, inductively coupled plasma optical emission spectrometry (ICP-OES) for S, ATR, solution and solid-state NMR and Raman spectroscopy. The interpretation of the complex spectra was aided by data for 2,4-dithiouracil obtained from 1H-1H COSY, DEPT-135, HMBC, and HMQC spectra. Additionally, the antimicrobial activity of these complex-es and the free ligands was evaluated against Gram-positive and Gram-negative bacteria, as well as yeasts.

Investigation of the methanol extract of the poroid fungus Fuscoporia torulosa resulted in the isolation of a novel triterpene, fuscoporic acid (1) together with inoscavin A and its previously undescribed Z isomer (2 and 3), 3,4-dihydroxy-benzaldehide (4), osmundacetone (5), senexdiolic acid (6), natalic acid (7), and ergosta-7,22-diene-3-one (8). The structures of fungal compounds were determined on the basis of NMR and MS spectroscopic analysis, as well as molecular modelling studies. Compounds 1, 6-8 were examined for their antibacterial properties on resistant clinical isolates, and cytotoxic activity on human colon adenocarcinoma cell lines. Compound 8 was effective against Colo 205 (IC50 11.65±1.67 µM), Colo 320 (IC50 8.43±1.1 µM) and MRC-5 (IC50 7.92±1.42 µM) cell lines. Potentially synergistic relationship was investigated between 8 and doxorubicin, which revealed a synergism between the examined compounds with a combination index (CI) at the 50% growth inhibition dose (ED50) of 0.521±0.15. Several compounds (1, and 6-8) were tested for P‐glycoprotein modulatory effect in Colo 320 resistant cancer cells, but none of the compounds proved to be effective in this assay. Fungal metabolites 2-5 were evaluated for their antioxidant activity using the oxygen radical absorbance capacity (ORAC) and DPPH assays. Compounds 4 and 5 proved to possess considerable antioxidant effect with EC50 0.25±0.01 (DPPH) and 12.20±0.92 mmol TE/g (ORAC). The current article provides valuable information on both chemical and pharmacological profiles of Fuscoporia torulosa, paving the way for future studies with this species.

The tetracyclic pyrido[4,3-b]carbazole olivacine and four of its oxygenated derivatives have been synthesized by a late-stage palladium-catalyzed Heck-type cyclization of the pyrrole ring as key step. In a test for inhibition of the growth of Mycobacterium tuberculosis 9-methoxyolivacine showed the most significant inhibiting activity against Mycobacterium tuberculosis with an MIC₉₀ value of 1.5 μM.

The results of the most recent investigation of triterpenoid-based antiviral agents effective namely in the HIV-1 and HSV-1 treatment were reviewed and summarized. Several key historical achievements are included to stress consequences and continuity in this research. Most of the agents studied belong into a series of compound derived from betulin or betulinic acid, and their synthetic derivative called bevirimat. A termination of clinical trials of bevirimat in the Phase IIb initiated a search for more successful compounds partly derived from bevirimat or designed independently of bevirimat structure. Surprisingly, a majority of bevirimat mimics are derivatives of betulinic acid, while other plant triterpenoids, such as ursolic acid, oleanolic acid, glycyrrhetinic acid or other miscellaneous triterpenoids, are relatively rarely involved in a search for novel antiviral agent. Therefore, this review article is divided into three parts based on the leading triterpenoid core structure.

Monoterpenes as natural products are the subject of increased attention in the search for new pharmacological agents because of their numerous biological activities including antifungal, antibacterial, antioxidant, anticancer, antispasmodic, hypotensive, vasodilating effects, etc. In vitro and in vivo studies reveal their antidepressant, anxiolytic, and memory-enhancing in experimental dementia and Parkinson’s disease effects. Chemical modification of natural substances by conjugation with various synthetic components is a modern method of obtaining new biologically active compounds. The discovery of new potential drugs among monoterpene derivatives is a progressive direction in experimental pharmacology and a promising approach to the therapy of various pathologies. Biologically active substances such as monoterpenes borneol, camphor, geraniol, pinene, and thymol, were used to synthesize compounds with different properties, including analgesic, anti-inflammatory, anticonvulsant, anti-depressant, anti-Alzheimer’s, anti-parkinsonian, antiviral and antibacterial (anti-tuberculosis). Myrtenal is a perspective monoterpenoid with therapeutic potential in various fields of medicine. Its chemical modifications often lead to new or more pronounced biological effects. As an example, conjugation of myrtenal with the known pharmacophore adamantane allows one to enhance some of its key properties. Myrtenal-adamantane derivatives exhibited a variety of beneficial properties – antimicrobial, antifungal, antiviral, anticancer, anxiolytic, and neuroprotective, which are worth examining in more detail and at length.

A series of derivatives of trans-3-(2,4,6-trimethoxy phenyl)-4,5-dihydro isoxazolo-4,5-bis(aroylcarbohydrazide) and of trans-3-(2,4,6-trimethoxyphenyl)4,5-dihydroisoxazolo-4,5-bis[carbonyl-(4’phenyl)thiosemi- carbazide (9) were synthesized from trans-3-(2,4,6-trimethoxyphenyl)-4,5-dihydro-4,5-bis(hydrazenocarbonyl) Isoxazole (8). The structures of the Compounds were elucidated by elemental and spectral (IR, NMR, and MS) analysis. The compound 9 show activity against some bacterial species. Whereas, no activity was observed for compounds 10a, 10b and 10c against all bacterial species. The antioxidant activity of new compounds has been screened. Compound 9 showed higher antioxidant activity using the DPPH and ATBS method.

Using the techniques of computer-aided drug design, the docking of Survivin and known active small molecules was simulated and then the key amino acid residue fragment of the target protein was analyzed. It led to the discovery of active groups capable of binding to the critical sites. Through the use of the natural product, Oleanolic Acid, as a lead compound, the introduction of the active groups onto the A-ring, and the modification of the carboxyl group at the C-28 position using esterification or amidation, twenty new Oleanolic acid derivatives had been designed and synthesized.A549 and SGC-7901 cells were used to screen the antitumor activity in vitro through the standard MTT method. The compounds, II₃, III₅ and Ⅳ_4, exhibited more potent cytotoxicity than positive drugs.

Recently, neglected and underutilized species (NUS) have deservedly come to the forefront of scientific interest because they can contribute to the human nutrition, due to the content of bio-active substances such as antioxidants. Despite the great diversity and rich tradition in use of Philippine NUS, the nutritional properties of many edible plants remain unexplored. The main objective of this study was to evaluate various parts of eleven NUS fruits and vegetables traditionally consumed in the Philippines, namely Allaeanthus luzonicus, Canarium ovatum, Dillenia philippinensis, Ficus pseudopalma, Flacourtia indica, Flacourtia inermis, Garcinia intermedia, Heliotropium arboreum, Posoqueria latifolia, Stelechocarpus burahol and Sterculia quadrifida for their total phenolic content (TPC) and in vitro antioxidant activity (DPPH and ORAC assays). The strongest antioxidant activity obtained in both assays were inflorescence of A. luzonicus (DPPH IC50 = 91.0 μg/mL, ORAC IC50 = 37.9 μg/mL) and fruit of S. burahol (DPPH IC50 = 253.7 μg/mL, ORAC IC50 = 32.2 μg/mL). These two species also had the highest TPC (202.1 and 133.0 µg GAE/mg extract, respectively). For all samples tested, the strong correlation was found between TPC and antioxidant activity. Based on our results, A. luzonicus and S. burahol have a promising potential as novel antioxidant rich food.

In recent years, growing attention has been directed towards the potential of plant extracts as great therapeutic agents in controlling oxidative stress and inflammation. Gymnema inodorum (Lour.) Decne, an indigenous plant locally grown in Northern Thailand, is known for its anti-diabetic activity. This study aims to explore the antioxidant properties and phenolic profile of column chromatographic fractionated G. inodorum leaf extract. The ethanolic-reflux extracts of G. inodorum leaves were subjected to column chromatography for the isolation of bioactive molecules. Total phenolic and flavonoid content were assessed using Folin–Ciocalteu and aluminium chloride colorimetric methods, respectively. Total antioxidant activity was evaluated by employing different antioxidant assays, including 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic)acid (ABTS) scavenging assay and ferric reducing antioxidant power (FRAP) assay. High-Performance Liquid Chromatography (HPLC) with a C18 column was employed to determine the level of gymnemic acid, while Liquid Chromatography Quadrupole Time-of-Flight/Mass Spectrometry (LC-QTOF/MS) was used to identify potential phenolic compounds. The three separated fractions indicating A, B, and C, exhibited remarkable antioxidant activity, with total phenolic content of 0.294 ± 0.056, 0.085 ± 0.039, and 0.227 ± 0.041 mg QE/mL, and total flavonoid content of 0.274 ± 0.050, 0.309 ± 0.110, and 0.384 ± 0.007 mg QE/mL, respectively. Fraction A exhibited the highest DPPH and ABTS scavenging activity, while fraction C demonstrated significantly higher ferric-reducing power. HPLC analysis revealed a highest concentration of gymnemic acid in fraction C (0.393 ± 0.003 mg/g) compared to fraction A (0.159 ± 0.003 mg/g) and fraction B (0.142 ± 0.000 mg/g). The LC-QTOF/MS phenolic screening showed seven potential phenolic compounds in fraction A, seven compounds in fraction B, and four compounds in Fraction C. A significant relationship is found between antioxidant potential and total phenolic content, suggesting that phenolic compounds are the major contributors to the antioxidant activity of G. inodorum.

Epidemiological studies have shown that consuming olive oil rich in phenolic bioactive compounds is associated with a lower risk of neurodegenerative diseases and better cognitive performance in aged populations. Since oxidative stress is a common hallmark of age-related cognitive decline, incorporating exogenous antioxidants could have beneficial effects on brain aging. In this review, we firstly summarize and critically discuss the current preclinical evidence and the potential neuroprotective mechanisms. Existing studies indicates that olive oil phenolic compounds can modulate and counteract oxidative stress and neuroinflammation, two relevant pathways linked to the onset and progression of neurodegenerative processes. Secondly, we summarize the current clinical evidence. In contrast to preclinical studies, there is no direct evidence in humans of the bioactivity of olive oil phenolic compounds. Instead, we have summarized current findings regarding nutritional interventions supplemented with olive oil on cognition. A growing body of research indicates that high consumption of olive oil phenolic compounds is associated with better preservation of cognitive performance, conferring an additional benefit, independent of the dietary pattern. In conclusion, the consumption olive oil rich in phenolic bioactive compounds has potential neuroprotective effects. Further research is needed to understand the underlying mechanisms and potential clinical applications.

The present study aims at valorizing Moroccan Henna (Lawsonia inermis) by developing healing formulations for cosmetic and therapeutic uses. For such a goal, the plant was collected from three locations in Southeastern Morocco (Alnif, Tafraoute Sidi Ali and Tazarine). Phytochemical anal-yses of aqueous extracts of Henna leaves was performed by determining phenolic compounds contents, flavonoids and tannins in the extracts. Then, specific formulations were prepared using aqueous extracts of L. inermis to assess their in vivo wound healing potential in Swiss Albino mice as animal model. Results disclosed that phenolic compound contents (13.48%), flavonoids (9.25%) and tannins (2.57%) are higher in Henna leaf extracts from Alnif, while Tazarine Henna aqueous extract was found to be richer in saponins (0.32%). Exclusion chromatographic analysis on Se-phadex G50 gel corroborates the obtained results and shows that Lawsone levels (Henna coloring agent) are higher in Henna collected from Alnif. Aqueous Henna leaf extracts, at a dose of 10% in petroleum jelly, have been tested for their ability to heal induced burns in mice. Healing moni-toring, carried out with Henna extracts on mice batches and those of two control batches (Mice batch treated with petroleum jelly alone and batch treated with petroleum jelly containing 1% flamazine), showed a great reduction in burnt surface with an accentuated contraction percentage (CP) and complete re-epithelialization duration (CRD) at 21 days in the three studied Henna-based formulations. These findings suggest the interest of potential development of Henna-based for-mulations, as source of phenolic compounds, for further dermatological, cosmetic and therapeutic applications.

Foods are mixed with saliva in the oral cavity and swallowed. During staying in the stomach, saliva is contentiously provided to mix with the ingested foods. Because a salivary component nitrite is protonated to produce active nitrous acid at acidic pH, the redox reactions of nitrous acid with phenolic compounds in foods become possible in the stomach. In the reactions, nitrous acid is reduced to nitric oxide (•NO), producing various products from phenolic compounds. In the products, stable hydroxybezoyl benzofuranone derivatives, which are produced from quercetin and its 7-O-glucoside, are included. Caffeic acid, chlorogenic acid, and rutin are oxidized to quinones and the quinones can react with thiocyanic acid derived from saliva producing stable oxathiolone derivatives. 6,8-Dinitrosocatechis are produced from catechins by the redox reaction, and the dinitrocatechins are oxidized further by nitrous acid producing the quinones, which can make charge transfer complexes with the dinitrosocatechin and can react with thiocyanic acid producing the stable thiocyanate conjugates. In this way, various products can be produced by the reactions of salivary nitrite with dietary phenolic compounds, and reactive and toxic quinones formed by the reactions are postulated to be removed in the stomach by thiocyanic acid derived from saliva.

A number of chemical modifications were carried out in order to synthesize new compounds based on the triterpenoid betulonic acid. Triazolation reactions were carried out for the synthesis of new 1,2,3-triazole derivatives based on betulonic acid. Chemical changes were made on the carbonyl group at the C-3 position of the initial molecule and on the carboxyl and hydroxyl groups at the C-28 position. Chromatographic methods were used to separate and purify the formed products. Spectroscopic (NMR-, mass-) methods were used to establish the structure of synthesized compounds. As a result of the chemical transformations carried out, a number of new derivatives of betulonic acid were obtained. All synthesized compounds were tested for antimicrobial and cytotoxic activity. As a result, compounds with pronounced antimicrobial activity were identified.

Supramolecular solvent (SUPRAS) has received increasing interest as an innovative, efficient, and green solvent for the effective extraction and separation of bioactive compounds from natural resources. However, studies on the use of SUPRAS for the extraction of phenolic components from plants, which are highly valued in food products due to their excellent antioxidant capacity, are still lacking. The present study developed a green ultrasound-assisted and efficient SU-PRAS method to simultaneously determine three phenolic acids in Prunella vulgaris by high-performance liquid chromatography (HPLC) and the experimental parameters were optimized in detail. The efficiency and antioxidant properties of the phenolic compounds obtained by different extraction methods were also compared. Under the optimal conditions, the extraction efficiency of SUPRAS, prepared with octanoic acid reverse micelles dispersed in ethanol-water, was substantially higher than conventional organic reagents. Moreover, this SUPRAS method also showed more significant antioxidant capacities. The confocal laser scanning microscopy (CLSM) images presented the spherical droplet structure of SUPRAS (A well-defined circle), which coincided with the position of the fluorescence position of phenolic acids. The phenolic acids were encapsulated in the vesicles by the SUPRAS droplets, which indicated the efficient extraction capacities of SUPRAS for the target compounds. Finally, combined with the CLSM method, the mechanism of the proposed method was further clarified, and the superior extraction performance of SUPRAS was theoretically demonstrated through molecular dynamics simulations. In comparison with conventional methods, the higher extraction efficiency of SUPRAS can be illustrated by the larger solvent contact surface area, more types of hydrogen bonds between extractants and supramolecular solvents, and stronger and more stable interaction forces. The results of the theoretical studies are in rational agreement with the experimental outcome.

The ribonuclease H (RNase H) active site of HIV-1 reverse transcriptase (RT) is the only viral enzyme not targeted by approved antiretroviral drugs. Using a fluorescence-based in vitro assay, we screened 65,239 compounds at a final concentration of 10 µM to identify inhibitors of RT RNase H activity. We identified 41 compounds that exhibited 50% inhibitory concentration (i.e., IC50) values < 1.0 µM. Two of these compounds, 2-(4-methyl-3-(piperidin-1-ylsulfonyl)phenyl)benzo[d]isothiazol-3(2H)-one (1) and ethyl 2-(2-(3-oxobenzo[d]isothiazol-2(3H)-yl)thiazol-4-yl)acetate (2), which both share the same benzisothiazolone pharmacophore, demonstrate robust antiviral activity (50% effective concentrations of 1.68 ± 0.94 µM and 2.68 ± 0.54, respectively) in the absence of cellular toxicity. A limited structure-activity relationship analysis identified two additional benzisothiazolone analogs, 2-methylbenzo[d]isothiazol-3(2H)-one (3) and N,N-diethyl-3-(3-oxobenzo[d]isothiazol-2(3H)-yl)benzenesulfonamide (4), which also resulted in inhibition of RT RNase H activity and virus replication. Compounds 1, 2 and 4, but not 3, inhibited the DNA polymerase activity of RT (IC50 values ~ 1 to 6 µM). In conclusion, benzisothiazolone derivatives represent a new class of multifunctional RT inhibitors that warrants further assessment for the treatment of HIV-1 infection.

Natural cytokinins are a promising group of cytoprotective and anti-tumor agents. In this research, we synthesized a set of novel cytokinin analogs with alkyl substituents at various positions of the aromatic moiety, as well as with oxygen-containing groups, and tested their antiproliferative activity in MDA-MB-231, A-375, and U-87 MG cell lines, and cytoprotective properties in H2O2 and CoCl2 models. Two amino-linked compounds were anti-proliferative with the ability to act synergistically with doxorubicin, and two carbamate-based ones were cytoprotective. According to the molecular docking data, anti-proliferation was based on the A2AR and APRT inhibition and cytoprotection on the CDK2 inhibition. The obtained results are promising for the development of novel anti-cancer therapeutics.

Schiff bases attract research interest due to their applications in chemical synthesis and medicinal chemistry. In recent years, benitrobenrazide and benserazide containing imine moiety, have been synthesized and characterized as promising inhibitors of hexokinase 2 (HK2) an enzyme overexpressed in most cancer cells. Both compounds possess a common structural fragment, a 2,3,4-trihydroxybenzaldehyde moiety connected through hydrazone or hydrazine linker with acylated on N’-nitrogen atom by serine or 4-nitrobenzoic acid fragment. To avoid presence of toxicophoric nitro group in benitrobenrazide molecule we introduced common pharmacophores 4-fluorophenyl or 4-aminophenyl substituents. Modification of benserazide regards an introduction of other endogenous amino acids instead of serine. Herein we report the synthesis of benitrobenrazide and benserazide analogues and preliminary results of inhibitory activity against HK2 evoked by these structural changes. The derivatives contain a fluorine atom or amino group instead of a nitro group in BNB, exhibited the most potent inhibitory effects against HK2 at a concentration of 1 µM, with HK2 inhibition rates of 60% and 54%, respectively.

As a part of our ongoing effort in the search for promising antileishmanial agents based on the thiochroman scaffold, we prepared a series of substituted 2H-thiochromenes. Thirty-three compounds were evaluated against intracellular amastigotes forms of L. (V) panamensis. Twelve compounds were active with EC₅₀ values lower than 40 μM, and among those three compounds displayed the highest antileishmanial activity with EC₅₀ values below 10 uM. Cytotoxicity was determined against human U-937 macrophages; thus, compounds having electrophilic alkenes (α,β-unsaturated carbonyl, or nitriles) displayed the highest antileishmanial activity but also moderate to high cytotoxicities. Based on SAR analysis, compounds 8d and 10, which differ only in the hydroxy group at C4, were selected as the most promising compounds in this library because good antiparasitic activity and Selectivity Index.

Plants have been used in alternative medicine for centuries in the treatment of many diseases with the metabolites they contain. The goal of this work was to investigate the phenolic profile, antioxidant capacity and biological activity of I. helenium subsp. pseudohelenium extracts. Phe-nolic (HPLC) substances in leaf ethanol (L-EtOH), leaf pure water (L-PW), root ethanol (R-EtOH), and root pure water (R-PW) extracts of Inula helenium subsp. pseudohelenium plant were investi-gated. Also, in vitro the antimicrobial (hollow agar), antioxidant (DPPH, ABTS.+, FRAP, CU-PRAC), antiproliferative (MTT assay against HT-29, MCF-7 and L-929), and DNA (Agarose gel electrophoresis) protective activities of the samples were examined. Although gallic acid was not detected in the extracts, the presence of curcumin was detected only in EtOH extracts. L-EtOH exhibited the best antimicrobial activity. According to the antioxidant results, it was found that the L-EtOH extract had an activity profile close to the standard antioxidants in general. It was also found that the L-EtOH extract stabilized the DNA by disrupting the scavenging effect of H2O2+DMSO. According to the antiproliferative activity results, EtOH extracts exhibited the strongest effect, especially against MCF7. When evaluated in general terms, it was found that L-EtOH extract showed better activity than other extracts. It is important to conduct more in vivo and in vitro studies after isolating the active components of extracts e.g. L-EtOH, which have good effects in terms of biological activity.

Ageing is associated with a decline in both Nrf2 activity and DNA repair efficiency, leading to the accumulation of DNA damage and an increased risk of cancer. Understanding the mechanisms behind the increased level of damaged DNA during ageing is crucial for developing interventions to mitigate age-related cancer risk and improve overall health in older individuals. (Poly)phenols are plant-derived bioactive compounds that undergo metabolism into simpler phenolic catabolites following ingestion. While these compounds have been associated with various health benefits, further analysis of their bioavailable catabolites is necessary. To this end, four phenolic catabolites derived from colonic microbiota were investigated for their ability to reduce DNA damage in response to oxidative challenge and modulate the Nrf2-Antixoidant Response Element pathway. Normal and adenocarcinoma colonocyte cell lines (CCD 841 CoN, & HT29 respectively) were exposed to sub cytotoxic concentrations (>10 µM,) of hydroxylated (4-hydroxybenzoic acid, 3-(3’-hydroxyphenyl) propionic acid) and non-hydroxylated (benzoic acid or 3-phenylpropionic acid) phenolic acids. Using the COMET assay, each catabolite demonstrated significant (p<0.001) geno-protective activity, albeit with varying potency. They also significantly modulated expression of key genes in the Nrf2-ARE pathway, including Nrf2, Heme oxygenase-1 (HO-1), and NAD(P)H dehydrogenase quinone 1 (NQO1). Hydroxylation of the phenolic acids appeared to have a limited effect with respect to bioactivity. Overall, the colon derived phenolic metabolites, when assessed at physiologically relevant concentrations, reduced DNA damage in both normal and adenocarcinoma colonic cells in response to oxidative challenge, mediated – at least in part via upregulation of the Nrf2-ARE pathway.

In recent decades, there has been a startling rise in the number of cancer patients worldwide, which has led to an amazing upsurge in the development of novel anticancer treatment candidates. On a positive note, arylpiperazines have garnered attention in cancer research due to their potential as scaffolds for developing anticancer agents. These compounds exhibit a diverse array of biological activities, including cytotoxic effects against cancer cells. Indeed, one of the key advantages of aryl piperazines lies in their ability to interact with various molecular targets implicated in cancer pathogenesis. Here, we focus on the chemical structures of several arylpiperazine derivatives, highlighting their anti-proliferative activity in different tumor cell lines. The modular structure, diverse biological activities, and potential for combination therapies of arylpiperazine com-pounds make them valuable candidates for further preclinical and clinical investigations in the fight against cancer. This review, providing a careful analysis of different arylpiperazine deriva-tives and their biological applications, allows researchers to refine the chemical structures to improve potency, selectivity, and pharmacokinetic properties, thus advancing their therapeutic potential in oncology.

Biomimetic materials are substances that replicate natural structures. There are several methods for producing such materials with highly developed surfaces from a wide range of polymers, but electrospinning is of particular interest due to its simplicity of implementation and the ability to modify the produced fibrous materials resembling structures found in living organisms. This study explores new biomimetic materials based on polyhydroxyalkanoates, specifically poly-3-hydroxybutyrate, modified with chlorophyll derivatives. The research investigates the impact of chlorophyll derivatives on the morphology, supramolecular structure, and key properties of nonwoven materials. The obtained results are of interest for the development of new biomimetic environmentally friendly materials for biomedicine with special properties.

A series of pyrazolopyrimidines derivatives 4– 11 were synthesized using 1-(6-(3-methoxyphenyl)-4-methylpyridazin-3-yl)-1H-pyrazolo [3,4-d] pyrimidin-4-amine 3 as a starting material. The detailed synthesis, structure assignments of the novel compounds based on chemical and spectroscopic evidence, spectroscopic data, pharmacological properties and molecular docking are reported. The pharmacological evaluation illustrated that many of these compounds have good analgesic, anti-inflammatory and antimicrobial activities.

A series of cysteine-based perfluoroaromatic (hexafluorobenzene (I) and decafluorobiphenyl (II) were synthesized and established as a chemoselective and available core to simple or more complex systems since small molecules to biomolecules with interesting properties. As proof of concept of the potential application of perfluorinated derivatives as non-cleavable linkers, some antibody-perfluorinated conjugates were prepared via thiol, demonstrating that the bioconjugation process doesn’t affect to the macromolecular entity. Besides, some molecular properties of synthesized compounds are evaluated using a combination of spectroscopic characterization (FT-IR and 19F-NMR chemical shifts) and theoretical calculations. Moreover, molecular Docking was also developed to predict cysteine-based hexafluorobenzene and decafluorobiphenyl derivatives’ affinity against topoisomerase Il and cyclooxygenase 2 (COX-2). The results suggested that mainly cysteine-based decafluorobiphenyl derivatives could be potential topoisomerase II α and COX-2 inhibitors, becoming potential anticancer agents and candidates for anti-inflammatory treatment.

This paper discusses the concept of fractional derivative with complex order from the application point of view. It is shown that a fractional derivative is hermitian, if and only if the order is real. The hermitian part of complex order derivatives behave like allpass filters with almost logarithmic phase.

This work aims to introduce a novel concept: the Riesz-Dunkl fractional derivatives, within the context of Dunkl type operators. A particularly noteworthy revelation is that when a specific parameter $\kappa$ equals zero, the Riesz-Dunkl fractional derivative smoothly reduces to both the well-known Riesz fractional derivative and the fractional second-order derivative. Furthermore, we introduce a new concept: the fractional Sobolev space. This space is defined and characterized using the versatile framework of the Dunkl transform.

Fourteen quinolizidine derivatives, structurally related to the alkaloids lupinine and cytisine and previously studied for other pharmacological aims, were presently tested for antiarrhythmic, inotropic, and chronotropic effects on isolated guinea pig heart tissues, and to assess calcium antagonism in comparison to amiodarone, lidocaine, procainamide, and quinidine. All compounds, but two, compared favorably with the reference drugs. Potent antiarrhythmic activity was observed for compounds (in increasing order) 4, 1, 6 and 5. The last compound N-(3,4,5-trimethoxybenzoyl)aminohomolupinane) was outstanding, exhibiting a nanomolar potency (EC50 = 0.017 µM) for the increase of threshold of ac-arrhythmia, and being devoid of antihypertensive activity against spontaneously hypertensive rats.

Human metapneumovirus is one of major causes of common cold among children, especially infants. Its key enzyme is RNA-dependent RNA-polymerase, which performs both replication and transcription, including capping and cap methylation. The goal of the work is to find possible inhibitors of RNA-dependent RNA-polymerase across the active compounds of Rosaceae plants. The candidates were selected by molecular docking to cap-transferring domain of RNA-polymerase (PDB ID: 4UCZ) in Autodock VINA. Among all the substances tested by docking, ellagic acid derivatives showed the most promising results (affinity values below -10 kcal/mol). Hence, they could be treated as possible candidate drugs against metapneumoviral infection after experimental examination. The main advantage of using these substances should be their low toxicity, which is quite uncommon for selective RNA polymerase inhibitors used in clinical practice. Occurrence of ellagic acid derivatives among the plants from Rosaceae family like raspberry could explain their effect during common cold.

We propose a methodology for the quantification of model risk in the context of credit derivatives pricing and CVA, where the uncertain or unmodelled parameter is often the correlation between rates and credit. We take the rates model to be Hull-White (normal) and the credit model to be Black-Karasinski (lognormal). We show how highly accurate analytic pricing formulae, hitherto unpublished, can be derived for CDS and extended to address instruments with defaultable Libor flows which may in addition be capped and/or floored. We also consider the pricing of a contingent CDS with an interest rate swap underlying. We derive explicit expressions showing how to good accuracy the dependence of model prices on the uncertain parameter(s) can be captured in analytic formulae which are readily amenable to computation without recourse to Monte Carlo or lattice-based computation. In so doing, we take into account the impact on model calibration of the uncertain (or unmodelled) parameter.

Biodiesel has several drawbacks, such as being prone to oxidation, having reduced stability, and having limited storage time. Antioxidants compatible with biodiesel are being used to address its drawbacks. Utilizing antioxidants effectively improves the quality of biodiesel. Enhancing the quality of biodiesel for use as a clean energy source benefits both the global economy and ecology. Therefore, we believe that our work will contribute to the advancement of the worldwide industry. The study used blends consisting of 20% biodiesel and 80% diesel fuel. Isatin-thiosemicarbazones were tested as additives in blends at a concentration of 3000 parts per million (ppm) using an oxifast device. Comparing them to the chemical antioxidant Trolox. FT-IR, DSC, and TGA were used to characterize these samples. DSC measured sample crystallization temperatures (Tc). Samples with antioxidants showed decreased values compared to the non-antioxidant diesel sample D100. Several DSC tests were conducted to determine the antioxidant strengths of various samples. The results showed that the FT-IR spectrum's antioxidant effect regions grow clearer with antioxidants. The extra antioxidant is effective. Biodiesel's oxidative stability improves with isatin-thiosemicarbazones at varying concentrations. The kinetics of thermal decomposition of isatin-thiosemicarbazones under non-isothermal conditions have been determined using the Kissinger, Ozawa, and Boswell techniques. The activation energies of compounds 1 and 2 were calculated 137–147 kJ mol^-1 and 173–183 kJ mol^-1, respectively.

The study of the morphology, thermal, and chemical stability of the fluorinated compounds was performed using Becke’s three-parameter hybrid functional approach with the correlation provided by Lee, Yang, and Parr and the cc-pVTZ basis set aiming to design low sensitivity, toxicity, instability, and proneness to decomposition or degradation over a short time high-energy materials. The most stable conformers of the compounds under study were selected based on their total energy. Their thermal and chemical stability was evaluated based on the binding energy per atom, chemical hardness, and softness. The oxygen-fluorine balance is assessed to evaluate the sensitivity of these new materials. The density, detonation pressure, and velocity of the selected conformers were theoretically obtained to reveal the influence of -CF3, -OCF3, and cyclic -O(CF2)nO- fragments on the energetic properties of nitroaromatics as well as their stability and resistance to shock stimuli. The results allow us to predict new multipurpose energetic materials with a good balance between power and stability. Referring to the results obtained, we recommend CF3N2, OCF3N2, C2F6N2, 1CF2N2/O2CF2N2, and 2CF4N2/O2C2F4N2 for practical usage because these compounds possess greater stability compared to tetryl and better explosive properties than TNT.

Two ferrocene derivatives, namely, 1,2-(tetramethylene)-ferrocene and 1,2,1’,2’-bis(tetramethylene)-ferrocene, were synthesized in a four-step reaction sequence starting from ferrocene. Friedel-Craft acylation of ferrocene with succinic anhydride gave mono- or bis(3-carboxypropinoyl)ferrocene depending on the stoichiometry of succinic anhydride. The reduction of the keto groups to methylene, followed by ring-closing using trifluoroacetic anhydride gave 1,2-(α-ketotetramethylene)-ferrocene or 1,2,1’,2’-bis(α-ketotetramethylene)ferrocene. The diastereomeric mixture of the latter diketones was separated by column chromatography, characterized by single-crystal X-ray analysis, and assigned their stereochemistry. Reduction of the keto groups to methylene under Clemmensen conditions gave homoannular mono- or bis(tetramethylene) ferrocene derivatives. The molecular structure of 1,2-(tetramethylene)-ferrocene revealed that the ipso carbon atoms of the cyclopentadienyl group are 0.023(3) Å farther away from Fe(II) compared to the remaining three carbon atoms. Both complexes exhibit lower half-wave oxidation potentials than ferrocene, possibly due to the electron-releasing effects of the tetramethylene bridges.

Rheumatoid arthritis (RA) is a complex illness with both hereditary and environmental compo-nents. Globally, in 2019, 18 million people had RA. RA is characterised by persistent inflammation of the synovial membrane that lines the joints, cartilage loss, and bone erosion. Phenolic molecules are the most prevalent secondary metabolites in plants, with a diverse spectrum of biological ac-tions that benefit functional meals and nutraceuticals. These compounds have received a lot of at-tention recently because they have antioxidant, anti-inflammatory, immunomodulatory, and anti-rheumatoid activity by modulating tumour necrosis factor, mitogen-activated protein kinase, nu-clear factor kappa-light-chain-enhancer of activated B cells, and c-Jun N-terminal kinases, as well as other preventative properties. This article discusses dietary polyphenols, their pharmacological properties, and innovative delivery technologies for the treatment of RA, with a focus on their possible biological activities. Nonetheless, commercialization of polyphenols may be achievable only after confirming their safety profile and completing successful clinical trials.

Inflammation mediators enhance the activity of connexin (Cx) hemichannels especially in the epithelial and endothelial tissues. As potential release route for injury signals like (oligo)nucleotides, Cx hemichannels may contribute to long lasting inflammation. Specific inhibition of Cx hemichannels may therefore be a mode of prevention and treatment of long lasting, chronic sterile inflammation. The activity of Cx hemichannels was analysed in N2A and HeLa cells transfected with human Cx26 and Cx46 as well as in Calu-3 cells using the dye uptake as functional assay. Moreover, possible impact of the bioactive phenolic agents CVB2-61 and CVB4-57 on the barrier function of epithelial cells was analysed using Calu-3 cells. Both agents inhibited the dye uptake in N2A cells expressing Cx26 (> 5 µM) and Cx46 (> 20 µM). In Calu-3 cells, CVB2-61 and CVB4-57 reversible inhibited the dye uptake at concentrations as low as 5 µM, without affecting the gap junction communication and barrier function, even at concentrations of 20 µM. While CVB2-61 or CVB4-57 maintained a reduced dye uptake in Calu-3 cells, an enhancement of the dye uptake in response to stimulation of adenosine signaling was still observed after removal of the agents. The report shows that CVB2-61 and CVB4-57 reversible block Cx hemichannels. Deciphering the interaction mechanisms with Cx hemichannels could allow further development of phenolic compounds to target Cx hemichannels for a better and safer use in treatment of pathologies that involve Cx hemichannels.

Umbu is a tropical fruit with high content of bioactive compounds. However, maturation causes significant losses on nutrient density reducing the nutritional value of this highly appreciated fruit. Thus, the objective of the present work was to encapsulate the Umbu fruit bioactive compounds using spray drying and identify the variables affecting the biomolecules preservation. A Box-Behnken experimental design with 3 factors was set varying inlet temperature, atomization flow rate, and maltodextrin concentration for process otimization. Then the powder physicochemical and chemical properties were characterized, and results were modeled using a polynomial equation. Results revealed that the droplet size and maltodextrin concentration had a significant influence on the conservation of the biomolecules. Drying kinetics favoring fast formation of a particle crust increases encapsulation efficiency. Bioactive compounds retention was achieved by increasing maltodextrin even at high temperatures, where a matrix is formed hindering chemical degradation. Process optimization was validated and revealed low inlet temperatures (122ºC), high atomization flow rate (5kg/h) and high maltodextrin concentration (20%) to be the most desirable conditions for bioactive compounds retention.

This study investigated the phenolic compounds of 15 Chrysanthemum morifolium Ramat cv. ‘Hangbaiju’, including 6 ‘Duoju’ and 9 ‘Taiju’ using high performance liquid chromatography. The antioxidant activities of these ‘Hangbaiju’ were estimated by DPPH, ABTS and FPAR assays. Results showed that a total of 14 phenolic compounds were detected in these flowers, including 3 mono-caffeoylquinic acids, 3 di-caffeoylquinic acids, 1 phenolic acid and 7 flavonoids. ‘Duoju’ and ‘Taiju’ possessed different concentration of phenolic compounds, and ‘Taiju’ exhibited higher caffeoylquinic acids and stronger antioxidant activities than ‘Duoju’. Caffeoylquinic acids showed a strong correlation with the antioxidant activities of the samples. Principal component analysis revealed an obvious separation between ‘Duoju’ and ‘Taiju’ using phenolic compounds as variables. Apigenin-7-O-glucoside, 3,5-di-O-caffeoylquinic acid, luteolin and acacetin were found to be the key phenolic compounds to differentiate ‘Duoju’ from ‘Taiju’.

The increase in fungal infections, accompanied by adverse effects and acquired resistance associated with the use of antifungal agents used for their clinical management, have facilitated the search for new substances with antifungal properties. Naphthoquinones have been investigated due to their multiple biological activities, including their significant antifungal potential. This study aimed at evaluating the antifungal potential of naphthoquinones against opportunistic fungi and dermatophytes and to assess the impact of a selected naphthoquinone on the formation of the cell wall, ergosterol membrane, and cellular membrane of Candida albicans ATCC 60193. Additionally, cytotoxicity in the MRC-(Medical Research Council-)5 cell lineage, Artemia salina, and tomato as well as arugula seeds was evaluated. The antifungal activity of four naphthoquinones was assessed using well-characterized fungal strains, the minimum inhibitory concentration (MIC) was determined applying the microdilution assay technique. Antifungal activity of the assessed naphthoquinones could be confirmed, particularly for 2,3-DBNQ (2,3-dibromo-1,4-naphthoquinone), which showed prominent antifungal activity (MIC of &lt;1.56 - 6.25 µg/mL) in all chosen test settings. However, its toxicity in MRC-5 cells (IC50 = 15.44 µM), a recorded 100% mortality in A. salina at a concentration of 50 µg/mL, as well as inhibition of 94.8% of the tomato seeds at a concentration of 400 µg/mL and inhibition of 64.1% of arugula seeds at a concentration of 200 µg/mL may limit hypothetical therapeutic applications. It was demonstrated that the likely mechanism of action of 2,3-DBNQ involves interfering with fungal membrane permeability, leading to increased leakage of nucleotides. This study adds to available knowledge on antifungal effects of naphthoquinones, especially of 2,3-DBNQ, against opportunistic yeasts and dermatophytes. However, the observed cytotoxicity in the MRC-5 cell lineage, A. salina, as well as tomato and arugula seeds highlights a need for further research to optimize the selectivity and safety profile of naphthoquinones like 2,3-DBNQ before potential clinical use may be assessed.

To study the feasibility and effect of compounding lignin and its derivatives to improve expansive soil, the physical properties, mechanical properties, and microstructure of the improved soil mixed with calcium lignosulfonate alone, calcium lignosulfonate and lignin fibers were investigated through indoor experiments and electron microscope scanning. Select samples with better performance for water stability tests, and discuss the improvement mechanism of expansive soil by combining macroscopic mechanical changes with microstructural characteristics. The research results show that the addition of calcium lignosulfonate can reduce the water content of the soil and enhance its strength of the soil. The overall performance is the best when the calcium lignosulfonate content is 3%. 3% calcium lignosulfonate compounded with 1.5% lignin fiber has the best all-around performance; the composite improved soil has a better pore-filling effect, the whole is more compact, and the connection between particles significantly enhances the strength, which greatly inhibits the development of cracks good water stability. Lignin and its derivatives compound improved expansive soil have better effect than traditional improvement methods, and have no pollution to the environment, which can provide a particular reference for engineering practice

To study the feasibility and effect of compounding lignin and its derivatives to improve expansive soil, the physical properties, mechanical properties, and microstructure of the improved soil mixed with calcium lignosulfonate alone, calcium lignosulfonate and lignin fibers were investigated through indoor experiments and electron microscope scanning. Select samples with better performance for water stability tests, and discuss the improvement mechanism of expansive soil by combining macroscopic mechanical changes with microstructural characteristics. The research results show that the addition of calcium lignosulfonate can reduce the water content of the soil and enhance its strength of the soil. The overall performance is the best when the calcium lignosulfonate content is 3%. 3% calcium lignosulfonate compounded with 1.5% lignin fiber has the best all-around performance; the composite improved soil has a better pore-filling effect, the whole is more compact, and the connection between particles significantly enhances the strength, which greatly inhibits the development of cracks good water stability. Lignin and its derivatives compound improved expansive soil have better effect than traditional improvement methods, and have no pollution to the environment, which can provide a particular reference for engineering practice.

A new series of 1,3,4-oxadiazoles derivatives was synthesized, characterized and evaluated for their in vitro and in vivo anti-thrombotic activity. Compounds (3a-3i) exhibited significant clot lysis with respect to negative control and reference drug streptokinase (30,000 IU) while enhanced clotting time (CT) values were observed (130-342 sec) for these tested compounds than the standard drug heparin (110 sec.). High affinity towards 1NFY with greater docking score was observed for the compounds (3a, 3i, 3e, 3d and 3h) than the control ligand RPR200095. In addition, very good inhibitory potential against factor Xa (F-Xa) was observed with higher docking scores (5612-6270) with ACE values (–189.68 to –352.28 kcal/mol) than the control ligand RPR200095 (Docking score 5192; ACE –197.81 kcal/mol. In vitro, in vivo and in silico results proposed that these newly synthesized compounds can be used as anti-coagulant agents.

Abstract: This study explores the antibacterial and antifungal activity of four floral honey types (12 samples) (A. seyal, Zizuphus spina-christi, Cucurbita maxima and A. nilotica) as related to their phenolic content, antioxidant capacity, and assessing their cytotoxic effects. The cup-plate agar diffusion assay was employed to examine the antimicrobial potency against different pathogens including Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Aspergillus niger and Candida albicans. Scavenging activity, total phenolic, flavonoid contents, and cytotoxicity were determined by the DPPH radical scavenging, Folin–Ciocalteu, spectrophotometry, and Brine shrimp lethality, bioassays respectively. All assessed honeys significantly inhibited the growth of the tested pathogens. Both Acacias honey exhibited high antioxidants with IC50: 6.68 and 9.08 mg/ml respectively for A. seyal and A. nilotica. The total phenol content varied from 5.75 to 67.95 mg (GAE)/100 g while the overall flavonoid content varied from 0.15 to 0.5mg (QE)/100 g. All honey types expressed no cytotoxicity effects one cell lines. Thus the study, supports the existing antimicrobial activity of honey. However, the strong antimicrobial activity of Cucurbita and Ziziphus honeys, with their corresponded poor antioxidant furtherly provides evidence that the high levels of phenolic substances in honeys is not always the only cause of their antimicrobial potency.

In searching for compounds with antioxidant and antifungal activity, our study focused on the subshrub species Empetrum rubrum Vahl ex Willd. (Ericaceae), commonly known as Brecillo or Murtilla de Magallanes. We measured the antioxidant activity of its methanolic extract (MEE) obtained from the aerial parts (leaves and stems). The antioxidant activity of MEE was evaluated in vitro by 2,2-Diphenyl-1-picrylhydrazyl (DPPH) free radical and 2,2′-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) cationic radical. Results were expressed in gallic acid and Trolox equivalents for DPPH and ABTS assays, respectively. The antioxidant activities, for the DPPH and ABTS assays, were also calculated as an inhibitory concentration of extract needed to inhibit 50% of the absorbance (IC50 value). The results of IC50 values measured by the DPPH and ABTS methods were 0.4145 mg mL-1 and 0.1081 mg mL-1, respectively. In relation to the antioxidant activity, the total phenolic content (TPC) in MEE was determined by the Folin-Ciocalteu method, and the presence of secondary metabolites groups, including phenolic compounds, was determined by using different standardized test procedures. Phenolic compounds contained in leaves, stems, and fruits of E. rubrum were determined qualitatively by means of high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS) analysis. The antifungal activity of MEE obtained from aerial parts of E. rubrum was tested against Rhizoctonia solani. In vitro, mycelial growth of this fungus was reduced from 90% to 100% in the presence of MEE.

Bipyridine and its related compounds are starting materials or precursors for a variety of valuable substances, such as biologically active molecules, ligands for catalysts, photosensitizers, viologens, and supramolecular architectures. Therefore, it is important to classify the synthesis methods and know their characteristics. Representative examples include the methods using homo- and heterocoupling of pyridine derivatives in the presence of catalyst. Because bipyridine compounds have a high ability to coordinate with metal centers, a decrease in catalytic activity and yield is often observed in the reaction system. To address this issue, the review provides insight into recent advances in bipyridine synthesis using metal complexes under both homogeneous and heterogeneous conditions. Moreover, the review also sheds light on strategies for bipyridine synthesis involving sulfur and phosphorous compounds. These alternative pathways offer promising avenues for overcoming challenges associated with traditional-catalyzed methods, providing a more comprehensive understanding of the synthesis landscape.

Breast cancer (BC) is the most common malignancy among women worldwide. In recent years, significant progress has been made in BC therapy. However, serious side effects resulting from the use of standard chemotherapeutic drugs, as well as the phenomenon of multidrug resistance (MDR), limit the effectiveness of approved therapies. Advanced research in the BC area is necessary to create more effective and safer forms of therapy to improve the outlook for individuals diagnosed with this aggressive neoplasm. For decades, plants and natural products with anti-cancer properties have been successfully utilized in treating various medical conditions. Anthracene derivatives are tricyclic secondary metabolites of natural origin that have been identified in plants, lichens, and fungi. They represent a few botanical families, e.g., Rhamnaceae, Rubia-ceae, Fabaceae, Polygonaceae, and others. The review comprehensively covers and analyzes the most recent advances in the anticancer activity of anthracene derivatives (emodin, aloe-emodin, hypericin, chrysophanol, rhein, and physcion) applied both individually, or in combination with other chemotherapeutic agents in in vitro and in vivo BC models.

An important parameter in the development of a new drug is the drug's affinity to the identified target (protein/enzyme). Predicting the ligand binding to the target (protein/enzyme) by molecular simulation would allow the synthesis to be restricted to the most promising compounds.A restricted hybrid HF-DFT calculation was performed in order to obtain the most stable conformer of each ligand and a series of DFT calculations using the B3LYP levels with 6-31G* basis set has been conducted. The docking studies of the quinolone compounds will be performed with the CLC Drug Discovery Workbench to identify and visualize the ligand-receptor interaction mode.

Terrestrial plant resources are becoming increasingly scarce; moreover, the development of science and technology has facilitated the exploration of marine ecosystems. We isolated and identified six novel (1–6) and six (7–12) known secondary metabolites of Alternaria sp MCCC 3A00467 by chromatographic and spectroscopic techniques and investigated their antitumor activities in human myeloma (U266), liver cancer (HepG2), and lung cancer (A549) cells by the MTT assay. Among these compounds, the new compounds 2, 3 and 4 exhibited excellent anticancer activities with IC₅₀ values of 21.98, 24.99 and 14.78 μg/mL, respectively. These compounds obtained from a marine source have the potential to be developed into novel anticancer drugs.

Resistance to the existing drugs and increasing numbers of diseases result in identifying new drug candidates with new forms of activity. Marine sources of alkylglycerols such as the liver oil Shark (SLO) mixture of certain species or rat fish (elasmobranch fishes) contain high levels of these compounds as a mixture of few species varying by length and unsaturation or saturation of the alkyl chain. They have multiple biological activities such as hematopoiesis stimulation, lowering radiotherapy-induced injuries, reducing tumor growth and improving vaccination efficiency. The synthesis of two Alkylglycerols (AKGs) containing at least one alkyne moiety in the alkyl chain has been reported. In this work, we describe the synthesis of others unknown AKGs based alkyne 1-O-(hexadec-11’-ynyl)-sn-glycerol 4 and 1-O-(octadec-9’-ynyl)-sn-glycerol 5 as analogues of bioactive ether lipids found in the SLO mixture.

Phytochemicals are gaining popularity due to their antioxidant effects and potential protection against inflammation, cardiovascular disease, and certain types of cancer. The retention of these phytochemicals during extraction must be maximized. This research focused on extracting bioactive compounds from Psidium guajava Linn leaves using solvent extraction (SE), microwave-assisted extraction (MAE), ultrasound-assisted extraction (UAE) with distilled water (DW) or 60% (v/v) ethanol/water (ET). Phytochemical screening demonstrated that all of the screening showed positive results in all extraction methods, except glycoside. There were no significant (p&gt;0.05) differences in total phenolic (TPC) and flavonoid content (TFC) during MAE, SE, and UAE in case of ET. However, SE shows better (p&lt;0.05) extraction of TPC and TFC than UAE and MAE in case of DW. ET shows better (p&lt;0.05) extraction of TPC and TFC than DW. Antioxidant analysis shows the same trend though both DPPH and FRAP values were higher in MAE and SE for ET and DW, respectively. MAE/ET showed the highest inhibitory activity and dose-dependent response using SW480 cell via MTT assay. HPLC and TLC analysis reveal the fingerprint of morin, might function as an anticancer agent. In conclusion, MAE/ET is the most efficient among the extraction techniques in terms of anticancer activity.

Enormous quantities of softwood and hardwood tree bark are generated yearly in the pulp and woodworking industry. Chemical compounds which can be found in bark extracts have important biological properties and therefore a high potential for using in the production of special formulations. In the present study, extraction of Picea abies bark with organosolv solvents was investigated to achieve a high yield of desirable compounds. For the extraction four different solvent ratios of ethanol and water were applied. The temperature range of extraction was set between 40 and 100 °C and stirring velocity of 400 rpm. Extractions were performed with a solid/liquid ratio of 1:20. Yields of phenolics, flavonoids and tannins were determined using gallic acid for total phenolic content (TPC), quercetin for total flavonoid content (TFC) and tannic acid for total tannins content (TTC) as calibration compounds. Qualitative analysis of phenolic constituents was performed after their derivatization, by gas chromatography coupled with mass spectrometry identification. The total yield of bark extract of 14.75 wt.% was achieved by using an ethanol/water ratio of 50% (v/v) and a temperature of 100 °C. Gas chromatography results show 9 aromatic carboxylic acids as phenolic acids and quercetin and (+)-catechin as flavonoid compounds. Highest concentrations of TPC = 3.21 mg gallic acid equivalent/g, TCF = 0.62 mg quercetin equivalent/g and TTC = 0.84 tannic acid equivalent/g were determined at the same process conditions by photometric method. This study determined the conditions for organosolv extraction of useful compounds and suggests that some of extractives, e.g., taxifolin and rhamnetin presented in the spruce bark extracts, have antiviral (SARS-CoV-2) effects. Therefore, this warrants further evaluation of the antiviral properties of spruce bark constituents.

To elucidate the chemical compositions of the sugar fall maple leaves, the methanol extracts were firstly fractionated by ethyl acetate and n-butanol respectively. The phenolic acids-rich fractions (ethyl acetate extracts) were further purified by various chromatographic columns including XAD macroporous resin, Sephadex LH-20, ODS and semi-preparative HPLC to yield the compounds. The isolated compounds were characterized by ¹H-Nuclear Magnetic Resonance (¹H-NMR), ¹³C-NMR, and high resolution electrospray ionisation mass spectral (HR-ESI-MS) spectroscopy. Twenty eight phenolics including fourteen flavonoids (1-14), five quinic acid derivatives (15-19), five galloyl tannins (20-24) and four other phenolic acids (25-28) were isolated and their structures were identified. The isolated compounds were evaluated for their antioxidant and α-glucosidase inhibitory activities. All of the phenolics constituents showed DPPH scavenging antioxidant activities. While, glycosides of quercetin and myricetin, galloyl tannins were showed promising α-glucosidase inhibitory activity. All of the compounds except 4, 11, 12 and 28 were isolated from sugar maple for the first time. Moreover, Compounds 9, 10, 14, 20, 21, 23, 25 and 26 were isolated from the Acer species for the first time.

In this study, the optimal condition for the extraction of antioxidants from the fruit Buah Mahkota Dewa (Phaleria macrocarpa) was determined by using Response Surface Methodology (RSM). The optimization was applied using central composite design (CCD) to investigate the three independent variables, namely extraction temperature (^oC), extraction time (minutes) and extraction solvent to-feed ratio (%v/v) on the responses of free radical scavenging activity (DPPH), ferric ion reducing power assay (FRAP), total phenolic content (TPC) and total flavonoid content (TFC).The optimal conditions for the antioxidants extraction were found to be extraction temperature (64^oC), extraction time (66 minutes) and solvent to-feed ratio (75 %v/v) with the highest percentage yield of DPPH, FRAP, TPC and TFC were 86.85%, 7.47%, 292.86 mg/g and 3.22 mg/g respectively. Moreover, the data were subjected to response surface methodology (RSM) and the results showed that the polynomial equations for all models were significant, did not show lack of fit, and presented adjusted determination coefficients (R²) above 99%, proving the yield of phenolic, flavonoid and antioxidants activities obtained experimentally were close to the predicted values and the suitability of the model employed in RSM to optimize the extraction conditions. Hence, in this study, the fruit from P.macrocarpa could be considered to have the strong antioxidant ability and can be used in various cosmeceutical or medicinal applications.

Neurodegenerative diseases (NDs) affect millions of people worldwide, and to date Alzheimer's and Parkinson's disease are the most common NDs. The risk of developing NDs increases dra-matically with age, and genetic and environmental factors can be crucial in their progression. The main feature of NDs is the abnormal presence of specific proteins that can lead to neuronal death, proteotoxic stress, and alteration of catabolic systems, which are major players in the processes of neurodegeneration and neuroinflammation. Despite research efforts to date, the therapies cur-rently in use for the treatment of NDs provide marginal therapeutic benefit, so the focus is now being direct toward the search of natural products that could be a valuable aid in combating these diseases, including the natural compound Andrographis paniculata (Ap) and especially its main constituent Andrographolide (Andro). Preclinical studies have shown that the aqueous extract of Ap is capable to modulate neuroinflammatory and neurodegenerative responses, determining a reduction in inflammatory markers and oxidative stress in various NDs. Therefore, in this review we will focus on the molecular mechanisms through which Ap and Andro are able to modulate the processes of neurodegeneration and neuroinflammation that are major causes of neuronal death and cognitive decline.

Inflammation is an important biological response to any tissue injury. The immune system responds to any stimulus, such as irritation, damage, or infection, by releasing pro-inflammatory cytokines. Overproduction of pro-inflammatory cytokines, including TNF-α and IL-1b, can lead to several diseases eg.,, cardiovascular diseases, joint disorders, cancer, and allergies. Emerging science suggests that whole grains may lower the markers of inflammation. Whole grains are a significant source of dietary fibres and phenolic acids that have inverse association with the risk of inflammation. The dietary fibres and phenolic acids composition of whole grains is very distinct over different grains. Whole grains (cereals and pseudo-cereals) are rich in both dietary fibres e.g., arabinoxylan, β-glucan and phenolic acids e.g., hydroxycinnamic acids, hydroxybenzoic acids, which are predominantly present in the bran layer. Although the biological mechanisms underlying widely reported association between whole grains consumption and a lower risk diseases are not fully understood. The modulatory effects of whole grains on inflammation also likely to be influenced by several mechanisms, including the effect of dietary fibres and phenolic acids, while some of these effects are direct, others involve gut microbiota, which transform important bioactive substances into more useful metabolites that moderate inflammatory signaling pathway. Thus, the aim of this review is two folded: first is to discuss the types of dietary fibres and phenolic acids commonly found in cereals and pseudo-cereals, and their health benefits observed in animal and human studies. Second, we review existing literature on the linkage between consumption of whole grains and markers of subclinical inflammation, the role of dietary fibres, phenolic acids, and gut microbiota on the anti-inflammatory activity of whole grains intake. Altogether, scientific data on the ant-inflammatory properties of whole grains are encouraging, further researches are needed to cover the gap between the emerging sciences of whole grains dietary fibres, phenolic acids and inflammation.

Environmental interventions and ecological adaptations harbor millions of valued substances and metabolites in plants which can be employed and commercialized for human benefits. Present study encompasses the untapped potential of pine needles of Indo-Himalayan region for the production of different metabolites and their pharmacological significance in terms of antioxidant and antimicrobial activity. Total phenolic and flavonoid content from the needles of ten pine species was quantified using three different solvent systems. Results revealed that out of 10 different selected Pinus species, Pinus taeda showed highest concentration of total phenolics, soluble-F phenolics and flavonoids content (approx.147.02 mg/g, 141.08 mg/g and 21.91mg/g respectively) as compared to other species. On the other hand P. greggii showed highest Bound-W phenolic content (approx.3.62mg/g). Among all the selected plant species, the needles of P.echinata exhibited the highest and P.thunbergii had the lowest ratio of total flavonoids to total phenolics. Most of these compounds were found to have effective antioxidant activities as well as antimicrobial activity, as estimated by oxygen radical absorbance capacity (ORAC) and disk diffusion test respectively.