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 We show how highly accurate analytic pricing formulae, hitherto unpublished, can be derived for CDS and extended to address instruments with defaultable Libor flows which may in addition be capped and/or floored.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.

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.

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.

Credit rationing, especially prevalent for smaller firms, impedes economic growth. A Central Bank aligned “not for profit” managed business to business “Stable-Coin” (“Synthetic Central Bank Digital Currency”) providing trade debt liquidity can lower small firm credit rationing. It raises growth by reducing monetary transmission imperfections consequent upon asymmetric information, commercial bank underwriting restrictions, market power dynamics and regulatory distortion. A simple framework is developed to contextualise small firm credit rationing and associated monetary transmission imperfections with broader credit flows into both the real and monetary sectors. Evidence is presented regarding US monetary transmission efficacy to firms, paving the way to proposing a trade debt business to business focused stable-coin to help close credit rationing gaps. Designed to minimise “moral hazard”, the proposed stable-coin provides an additional monetary transmission channel that supplies interest free trade debt funding to firms to support economic activity and raise growth. In addition to helping close the small firm financing gap, the stable-coin provides policy makers with an additional contra-cyclical monetary transmission instrument to minimise real economic disruption consequent upon financial system crises and liquidity events.

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%.

This paper shows the influence of CCP’s collateralization on the pricing of the Credit Default Swaps (CDS). A narrowly variant in the way the CDS seller decides over the resources in the settlement comes with a substantial change on the elements that determine the price of the CDS.

This study considers the values of the credit payments that are made at random values for both payment size and number. The simultaneous existence of the two random variables increases the total value of the volatility of the payment process. The dependence for the simultaneous influence of the two random variables is derived by applying conditional probabilistic formulations. Formal relations apply to animal husbandry credit payments. The credit policy was analyzed for the cases of regular payments and with a stochastic number of payments. A recommendation for the upper level of credit payments is proposed based on a model predictive approach using historical payment data. A credit management algorithm is derived, in which decision-making for credit payments is formally derived and numerically discussed. The application of derived quantitative relations is empirically applied to real data on animal husbandry. The recommendations from the dependencies obtained allow a reduction in the mean values of credit payments, which correspond to a reduction in the credits used for business management, without a change in business policy.

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.

This study aims to identify the model that best approximates the credit spread that should be fixed on debt instruments issued by both public and private companies, considering the particularities of the Mexican market. Five models were analyzed: Merton's [1], those proposed by Denzler et al., the one presented in this paper, which includes the conformable derivatives, taking as a reference the change of variable made by Morales-Bañuelos et al., and the Corporate Default Risk Model (DRSK) for Publics Firms of Bloomberg [4]. The required financial information was obtained from the Bloomberg platform, from which the probabilities of default, credit spreads, and credit ratings for each company in the sample under the model (DRSK) were extracted directly. Likewise, the program developed by Moody's K.M.V. was used to obtain the EDF (Expected Default Frequencies). It was concluded that the Modified Merton model approximates to a greater extent the credit spreads that fix on a prime rate on the loans granted to the Mexican non-financial companies.

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.

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.

Commercial banks usually classify customers according to their credit reports when making loans. In this study, we put our focus on classifying customers based on their credit reports from the People's Bank of China (PBC). Since there are no target labels of users in the credit report of the People's Bank of China, we put forward the fuzzy clustering method for the initial label, and then Construct ant colony search to optimize intelligent recognition. Finally, this study uses SVM, BP neural network, and random forest to classify users and compare their results. The research re-sults indicate that using ant colony clustering algorithm and random forest for classification is the most effective method with the PBC credit reports.

The paper is an investigation on the impact of financial markets on the volatility of green bonds credit risk component, measured by the option-adjusted spread/swap curve (OAS) of the Global Bloomberg Barclays MSCI Green Bond Index, for both the non and pandemic periods. For these purpose, after observing the dynamic joint correlations between all the variables through a DCC-GARCH, we adopt GARCH(1,1) and EGARCH(1,1) models, putting the OAS as dependent variable. Our main results show that the conditional variance parameters are significant and persistent in both times, testifying the overall impact of the other markets on the OAS. In more detail, we highlight that the gamma in the two EGARCH models is positive: so the “green” credit risk volatility is more sensitive to positive shocks than negative ones. With reference to the conditional mean, we note that if during the non pandemic time only the stock market is significant, during the pandemic also conventional bonds and gold are impacting. To the best of our knowledge this is the first study that analyzes the specific credit risk component of green bond yields: we deem our findings useful to observe the change of green bonds creditworthiness in a complex market context.

Export participation and restricted access to external formal credit are two factors attracting meticulous attention from researchers and policymakers, especially in developing countries. Exploring the interactive relationship of these factors in both the static and dynamic models is the purpose of this study. The study uses data sets from small and medium-sized manufacturing enterprises (SMEs) in Vietnam for the period 2009 - 2015. The instrumental variable approach is implemented to deal with the endogenous variable problem in the model. The results show an effect of credit constraint on the firms’ exporting status, and continuous exports are likely to reduce the limit of credit constraint.

The current study explores the problem of illiquidity in the corporate bond market and examines a broad set of liquidity proxies through empirical investigation. Purpose: The purpose of this paper is to give solution to the global issue of illiquidity in the corporate bond market. The problem is identified by many researchers and this paper attempts to find out the viable solution of the "fungibility route" as an alternative to the "liquidity route". Design/ Methodology: An Analysis of a sample size of 2,34,772 trade data of corporate bonds and a sample size of 2,00,607 trade data of G-securities is done to identify the problem. Findings / Solution proposed: A mathematical model based on credit risk differential and sensitivity differential is proposed to find out the fair value at which an illiquid bond can be swapped by a liquid bond. To arrive at the fair value of the illiquid bond, we have calculated risk adjusted discount rate using modified duration and credit risk differential. With our solution, it is possible to enhance the liquidity of the bond not directly but through fungibility route. Originality: the research is first of its kind in which solution is given to the global problem of corporate bond illiquidity. To execute the trade in the fungibility route, proposed parties involved are the Fungibility platform, the initiator, and the bidder. The derived fair value would facilitate trade and serve as an exit strategy for illiquid bond holders worldwide.

This article presents a comprehensive framework for valuing financial instruments subject to credit risk. In particular, we focus on the impact of default dependence on asset pricing, as correlated default risk is one of the most pervasive threats in financial markets. We analyze how swap rates are affected by bilateral counterparty credit risk, and how CDS spreads depend on the trilateral credit risk of the buyer, seller, and reference entity in a contract. Moreover, we study the effect of collateralization on valuation, since the majority of OTC derivatives are collateralized. The model shows that a fully collateralized swap is risk-free, whereas a fully collateralized CDS is not equivalent to a risk-free one.

The use of credit cards and online banking is expanding exponentially. As more individuals use debit cards, credit cards, and internet banking, the likelihood of falling victim to various forms of fraud also rises. Due to ignorance, credit card company customers have provided their card details, personal information, and one-time password to an unknown bogus caller on several occasions in the recent past. One of the biggest issues facing financial institutions and customers alike is credit card theft. It may result in large financial losses and harm to the financial institution's image. While there are several ways to identify credit card fraud, one of the best is machine learning.By using past data, machine learning algorithms may be trained to recognize trends and abnormalities that point to fraud. The state-of-the-art in machine learning for credit card fraud detection is reviewed in this study. Numerous research on the same subject have been conducted in the past with a variety of well-known machine-learning techniques. However, with a grasp of the notion of hybrid machine learning, we will now examine how well hybrid machine learning performs on the same problem statement.

In the era of digital advancements, the escalation of credit card fraud necessitates the development of robust and efficient fraud detection systems. This paper delves into the application of machine learning models, specifically focusing on ensemble methods, to enhance credit card fraud detection. Through an extensive review of existing literature, we identified limitations in current fraud detection technologies, including issues like data imbalance, concept drift, false positives/negatives, limited generalisability, and challenges in real-time processing. To address some of these shortcomings, we propose a novel ensemble model that integrates a Support Vector Machine (SVM), K-Nearest Neighbor (KNN), Random Forest (RF), Bagging, and Boosting classifiers. This ensemble model tackles the dataset imbalance problem associated with most credit card datasets by implementing under-sampling and the Synthetic Over-sampling Technique (SMOTE) on some machine learning algorithms. The evaluation of the model utilises a dataset comprising transaction records from European credit card holders, providing a realistic scenario for assessment. The methodology of the proposed model encompasses data pre-processing, feature engineering, model selection, and evaluation, with Google Colab computational capabilities facilitating efficient model training and testing. Comparative analysis between the proposed ensemble model, traditional machine learning methods, and individual classifiers reveals the superior performance of the ensemble in mitigating challenges associated with credit card fraud detection. Across accuracy, precision, recall, and F1-score metrics, the ensemble outperforms existing models. This paper underscores the efficacy of ensemble methods as a valuable tool in the battle against fraudulent transactions. The findings presented lay the groundwork for future advancements in the development of more resilient and adaptive fraud detection systems, crucial as credit card fraud techniques continue to evolve.

In this systematic review of the literature on using Machine Learning (ML) for credit risk prediction, we raise the need for financial institutions to use AI and ML to assess credit risk, analyzing large volumes of information. We posed research questions about algorithms, metrics, results, data sets, variables, and related limitations in predicting credit risk. We searched renowned databases to answer them and identified 52 relevant studies with the credit industry microfinance. Challenges and approaches in credit risk prediction using ML models we identified, difficulties with the implemented models such as the black box model, the need for explanatory artificial intelligence, the importance of selecting relevant features, addressing multicollinearity, and the problem of the imbalance in the input data. By answering the questions, we identified that the Boosted Category is the most researched family of ML models; the most commonly used metrics for evaluation are Area Under Curve (AUC), Accuracy (ACC), Recall, precision measure F1 (F1), and Precision; Research mainly uses public data sets to compare models, and private ones to generate new knowledge when applied to the real world. The most significant limitation identified is the representativeness of reality, and the variables primarily used in the microcredit industry are related data to the demographic, the operation, and payment behavior. This study aims to guide the developers of credit risk management tools and software towards the existing offer of ML methods, metrics, and techniques used to forecast it, thereby minimizing possible losses due to default and guiding risk appetite.

Various sudden shifts in financial market conditions over the past decades have demonstrated the significant impact of market structural breaks on firms' credit behavior. To characterize such effect quantitatively, we develop a continuous-time modulated Markov model for firms' credit rating transitions with the possibility of market structural breaks. The model takes a semi-parametric multiplicative regression form, in which the effects of firms' observable covariates and macroeconomic variables are represented parametrically and nonparametrically, respectively, and the frailty effects of unobserved firm-specific and market-wide variables are incorporated via the integration form of the model assumption. We further develop a mixtured-estimating-equation approach to make inference on the effect of market variations, baseline intensities of all firms' credit rating transitions, and rating transition intensities for each individual firm. We then use the developed model and inference procedure to analyze the monthly credit rating of U.S. firms from January 1986 to December 2012, and study the effect of market structural breaks on firms' credit rating transitions.

In this work, we apply ensemble formalism to a geometric agents model to study the effect of saving propensity in a system with money, credit, and debt. We calculate the partition function to obtain the total money of the system, with which we give an interpretation of the economic temperature in terms of the different payment methods available to the agents. We observe an interplay between the fraction of money that agents can save and the debt that can be financed. We also observe that the system’s entropy increases as the saved proportion increases and increases, even more, when debt is present.

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.

This study examined the tail dependency structure of sovereign credit risk and three global risk factors in BRICS countries using copulas approach, which is known for its ability to provide the “true” tail correlation based on the correct marginal distribution. The empirical results show that global market risk sentiment comoves with sovereign CDS spreads across BRICS countries under extreme market events, with Brazil having the highest co-dependency followed by China, Russia, and South Africa. Furthermore, oil price volatility is the second biggest risk factor correlated with sovereign CDS spreads for Brazil and South Africa while exchange rate risk exhibits very small co-dependence with sovereign CDS spreads under extreme market conditions dominated by tail events. On the contrary, exchange rate risk is the second largest risk factor co-moving with China and Russia’s sovereign CDS spreads while oil price volatility exhibits the lowest co-dependence to CDS in these countries. Between oil price and currency risk, evidence of single risk factor dominance is found for Russia where exchange rate risk is largely dominant. These results suggest that BRICS policymakers might consider financial sector regulations that mitigate risks spill-over such as targeted capital controls when markets are distressed.

In no-tillage systems, there is an accumulation of crop residues (CR) which plays an important role in available of soil-N. A study was set up to provide information regarding the CR N credit, and the influence of N mineral fertilizer. An incubation was run in a loam soil with addition of a similar rate of residue (10 Mg ha-1; sugarcane, soybean, and brachiaria) and N mineral fertilizer (urea; 120 kg N ha-1). After the stabilization of biological activity, soil and remaining residues were collected, and N monitored. Results showed that the N credit was positive with application of soybean, sugarcane, and brachiaria. There was an expressive performance of soybean N credit represented by a positive balance, and a reduction from 2.49 to 0.9 g kg-1 of N in residue, with direct increase of 90% of soil-N. There is no need of N fertilizer to potentialize the soybean N credit, but it is requested to potentialize N credit of brachiaria and sugarcane. The urea demonstrated be a good enhancer of brachiaria N credit, but it was not adequate to sugarcane residues. Based in our result, the accumulation and incorporation of CR can be considered as a N credit with positive contribution in soil-N.

Stemming from the urgency of the actual situation, commercial banks need an effective credit risk management tool to limit risks. The authors went to survey, study and propose a set of factors affecting the ability of debt repayment of individual customers and conducting surveys. The topic uses data sets including 240 observation samples. Using the SPSS software to clean data and run the model based on Maddala's Binary logistics regression published in 1984 to find out the impact of each individual element of customers affecting their ability to repay such debts. Come on. The authors also specify the order of influence of each factor determining the ability to repay individual customers, thereby helping bank managers have a better visual view to make decisions for borrowing accurately, limiting risks.

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.

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.

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.

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.

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.

Despite the use of commercial forest carbon protocols (CFCPs) for more than two decades, claiming ~566 MMtCO₂e and a market value of ~USD $15.7 billion, comparative analysis of CFCP methodology and offset results is limited. In this study, five widely used biometric-based CFCPs are characterized, and common characteristics and differences are identified. CFCP claims of net forest carbon sequestration are compared with results of directly measured CO₂ by eddy covariance, a meteorological method integrating gross vertical fluxes of forest and soil carbon, and the only alternative non-biometric source of net forest carbon sequestration data available. We show here that CFCPs share a structural feature delimiting forest carbon values by zero-threshold carbon accounting (gC m^-2 ≤ 0), a pattern opposite to natural emissions of forest CO₂ exchange based on direct measurement and a fundamental biological constraint on net forest carbon storage (i.e., soil efflux, ecosystem respiration). Exclusion of forest CO₂ sources to the atmosphere precludes net carbon accounting, resulting in unavoidable over-crediting of CFCP project offsets. CFCP carbon results are significantly different from global forest CO₂ net ecosystem exchange population results (FluxNet2015 gC m^-2) at the 95% to 99.99% confidence levels, inferring an annual median error of ~247% (gC m^-2), consistent with over-crediting. Direct CO₂ measurement provides an urgently needed alternative method for commercial forest carbon products that has the potential to harmonize global markets and catalyze the role of forests in managing climate change through nature-based solutions.

The residential sector in the United States is in need of comprehensive policy-making reforms that concurrently address housing affordability and environmental sustainability. This study investigates the feasibility of state-wide zero-energy affordable housing by analyzing historical data on climate, energy use, and solar system costs in the Commonwealth of Virginia. The hypothesis examined is that the net present cost of implementation of rooftop residential solar systems to achieve zero-energy Low-Income Housing Tax Credit (LIHTC) buildings is lower than the discounted present cost of energy of otherwise identical conventional buildings that run without renewable energy generation systems. The authors propose a generalizable framework for analyzing the feasibility of achieving region- or state-wide zero-energy LIHTC developments. To validate the framework, the authors employ a longitudinal sample of monthly energy use data from 2013-2016 obtained from 310 residential units of 15 LIHTC developments across the state. Based on statistical regression analysis, energy simulation, and simulation-based risk analysis, the authors find that the net present value of zero-energy LIHTC investments can be positive with a low risk. The investment value varies often depending on the zero-energy building definition, weather characteristics, retail price of electricity, and incentive rate. This study can help housing policymakers and industry professionals analyze and benchmark the feasibility of innovative zero-energy housing policies and projects.

We examine the profitability of the momentum and contrarian strategies in three South Asian markets i.e. Bangladesh, India and Pakistan. We also analyze, whether credit risk influences momentum and contrarian return for these markets from 2008 to 2014. We use Distance-to-default (DD) of Kealhofer, McQuown and Vasicek (KMV) model as a measure of credit risk. We calculate the credit risk and form the momentum and contrarian strategies of the firms on the basis of high, medium and low risk. We find that in all three markets, the momentum and contrarian returns are significant for medium and high credit risk portfolios and no momentum and contrarian returns for low credit risk portfolios.

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.

The ultimate goal of this paper was to examine the degree of elasticity between two variables, namely, agricultural credit and agricultural growth, in Angola in the period 2003–2022. Time series data were fitted into the ARDL test using various econometric techniques such as the ADF stationarity test, Granger causality and the ordinary least squares method as well as a vector error correction model (VECM) to analyze the relationship between agricultural credit and agricultural economic growth, showing a causal relationship. Both the impacts through elasticities and the optimal point existing in this relationship were estimated. It was concluded that the impact of agricultural credit on agricultural GDP was 14.41%. Granger causality shows signs of a positive linkage between agricultural credit and agricultural GDP. However, there is a causal relationship between agricultural credit and agricultural GDP, in a unidirectional aspect. This result is consistent with most of the earlier studies reviewed in the literature, confirming that credit-oriented monetary policies can boost economic growth and, consequently, development in Angola. It is important for agricultural credit systems to be designed in a way that ensures equitable access, fair interest rates, and appropriate risk management mechanisms. Additionally, monitoring and evaluation mechanisms should be in place to assess the environmental and social impacts of credit programs on agricultural sustainability. It is worth noting that this is a first-of-a-kind study on the matter of the Angolan credit experience, specifically for the agricultural sector. Angola is still searching for a sustainable credit model that could be used as a catalyzer to boost growth and contribute to economic development.

The stress testing methodology should be implemented and applied to the entity's overall financial system at least annually, and if the organization operates in a volatile economy, it should be performed at least twice a year. Finally, managers should include regular training and development sessions for relevant employees of their organization to be fully informed and more informed and informed, considering the evolving science, theory and practicality of a discrete range of stress testing mechanisms that can be appropriately applied to overall financial framework and system of multiple financial institutions and banks. In addition, stress testing is essentially a methodology that collects and analyzes certain future macro-prudential and micro-prudential economic drivers and indicators, the primary purpose of which is to assess the future financial and economic well-being, level of growth and status quo of a financial institution, bank, organization, credit institution or economy or the nation as a whole. In addition, several of these reviews were specifically focused and incorporated into the paper, which substantially and broadly discussed and summarized the importance, feasibility and implementation and conclusions of different stress testing approaches for financial institutions and banks, especially in European and Chinese countries. region. with the primary intention of assessing the future financial and economic well-being, level of growth and status quo of a group of financial institutions, banks, organizations, credit institutions or the economy or the nation as a whole. In addition, several of these reviews were specifically targeted and incorporated into a paper that substantially and broadly discussed and summarized the importance of the feasibility and implementation and conclusions of different stress testing approaches for financial institutions and banks, especially in European and Chinese countries. region. with the primary intention of assessing the future financial and economic well-being, level of growth and status quo of a group of financial institutions, banks, organizations, credit institutions or the economy or the nation as a whole. In addition, several of these reviews were specifically focused and incorporated into the paper, which substantially and broadly discussed and summarized the importance, feasibility and implementation and conclusions of different stress testing approaches for financial institutions and banks, especially in European and Chinese countries. region. the level of growth and status quo of the financial institutions, banks, organizations, credit institutions or the economy or the nation as a whole. In addition, several of these reviews were specifically focused and incorporated into the paper, which substantially and broadly discussed and summarized the importance, feasibility and implementation and conclusions of different stress testing approaches for financial institutions and banks, especially in European and Chinese countries. region. the level of growth and status quo of the financial institutions, banks, organizations, credit institutions or the economy or the nation as a whole. In addition, several of these reviews were specifically focused and incorporated into the paper, which substantially and broadly discussed and summarized the importance, feasibility and implementation and conclusions of different stress testing approaches for financial institutions and banks, especially in European and Chinese countries.

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.

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.

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.

The research explores the impact of financial indicators on the credit ratings of companies listed on the S&P 500, employing a Sys-GMM Model to address endogeneity concerns. The study investigated three independent variables categorized as market and survival factors alongside with seven control variables sourced from leverage, liquidity, interest coverage, profitability, market, survival, and macroeconomic domains. The sample comprised 2398 observations from Capital IQ Pro, spanning nine years (2013 to 2021) and encompassing 240 public companies. The findings suggest that neither Tobin's Q (TQ) and Total Shareholder Return (TSR) lack significant correlations with credit ratings, implying that stock market performance and total shareholder return do not directly impact credit ratings. In contrast, the Altman Z-score (AZS) emerged as a significant predictor, indicating its importance in assessing credit risk. These insights enhance understanding of financial indicators' impact on credit ratings, aiding financial institutions and companies in prudent lending and financing decisions.

The service sector, whose value has started to increase in recent years, has gained momentum with the acceleration of economic developments especially after the 2000s in Turkey. In a world where competition is increasing and social purchase perception is changing, companies started to differentiate in the service sector to create a competitive advantage. Companies that would like to grow in the industry and aspire to a greater proportion need credit to extend. There are many factors to consider in order to allocate the credit. Banks make financial and non-financial analysis to make credit decisions. This study has been prepared to assess the effect of financial and non-financial features of middle segment companies that need credit in the service sector on the credit decision to be allocated by banks. The group of variables that explain the credit decision at the highest level in these companies are non-financial variables.

Survival models have become popular for credit risk estimation. Most current credit risk survival models use an underlying linear model. This is beneficial in terms of interpretability but is restrictive for real-life applications since it cannot discover hidden nonlinearities and interactions within the data. This study uses discrete time survival models with embedded neural networks as estimators of time to default. This provides flexibility to express nonlinearities and interactions between variables, and hence allows for models with better overall model fit. Additionally, the neural networks are used to estimate Age-Period-Cohort (APC) models so that default risk can be decomposed into time components for loan age (maturity), origination (vintage) and environment (e.g., economic, operational and social effects). These can be built as general models, or as local APC models for specific customer segments. The local APC models reveal special conditions for different customer groups. The corresponding APC identification problem is solved by a combination of regularization and fitting the decomposed environment time risk component to macroeconomic data, since the environmental risk is expected to have a strong relationship with macroeconomic conditions. Our approach is shown to be effective when tested on a large publicly available US mortgage data set. This novel framework can be adapted by practitioners in the financial industry to improve modelling, estimation and assessment of credit risk.

This paper examines the influence of informal competition on SMEs innovation in the Eastern European transition economies. It investigates whether credit constraints mediate this relation. SMEs innovation is presented through four measures: Product innovation, Process innovation, Radical innovation and Green innovation. Using the BEEPs VI that covers the period from 2018-2020, we show that informal competition affects positively the product, process and radical innovation. Yet, it has a non-significant effect on green innovation. Besides, the informal sector increases SMEs credit constraints, which indirectly leads to less corporate innovation. The negative indirect effect restrains the positive direct effect. Hence, a partial mediation effect of credit constraints on the informal competition and the innovation proxies is reported with the exception of green innovation.

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.

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.

This study is the first to examine whether the performance of credit rating, one of the most important data-based decision-making of banks, can be improved by using banking system log data that is extensively accumulated inside the bank for system operation. This study uses the log data recorded for the mobile app system of Kakaobank, a leading internet bank used by more than 14 million people in Korea. After generating candidate variables from Kakaobank's vast log data, we develop a credit scoring model by utilizing variables with high information values. Consequently, the discrimination power of the new model compared to the credit bureau grades was significantly improved by 1.84% points based on the Kolmogorov–Smirnov statistics. Therefore, the results of this study imply that if a bank utilizes its log data that have already been extensively accumulated inside the bank, decision-making systems, including credit scoring, can be efficiently improved at a low cost.

In this paper, we use the Principal Components Logistic Regression as a technique to reduce the variables being used in Credit Scoring Modeling. Specifically, we construct two models in which greek enterprises are classified, through their credit behavior and we evaluate them, relying on real data. In general, we propose a general way to use PC Regression, in case that we have high correlations and categorical variables in the sample.

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.

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 <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.

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.

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.

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.

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.

Green credit policy as an important tool to guide China's sustainable economic development, how to effectively play the function of capital deployment and improve the efficiency of industrial green innovation is an important issue facing the construction of ecological civilization. This paper uses China's Green Credit Guideline introduced in 2012 as a quasi-natural experiment , based on relevant panel data of industries from 2007 to 2018, uses the Super-SBM model including non-expected output to measure the green innovation efficiency of 35 industries in China, and constructs the PSM-DID model to explore how green credit policy impact on the green innovation efficiency of heavily polluted industries, the results show that : green credit policy significantly contributes to green innovation efficiency of heavily polluted industries with a lag. Further study finds that green credit policy pushes heavily polluted industries to improve green innovation efficiency by increasing financing cost and R&D investment; meanwhile, the heterogeneity test shows that the higher the state-owned share of industry, the greater the promoted effect of green credit policy on green innovation efficiency of heavily polluted industries. Finally, in order to accelerate the implementation of green credit policy and promote the green innovation efficiency of heavily polluted industries, relevant countermeasures are proposed from three aspects: banks, enterprises and government.

Recently, pharmaceutical research has been focused on the design of new antibacterial drugs with higher selectivity towards several strains. Major issues concern the possibility to obtain com-pounds with fewer side effects, at the same time effectively overcoming the problem of antimi-crobial resistance. Several solutions include the synthesis of new pharmacophores starting from piperazine or morpholine core units. Mass spectrometry-based techniques offer important sup-port for the structural characterization of newly synthesized compounds to design safer and more effective drugs for various medical conditions. Here, two new piperazine derivatives and four new morpholine derivatives were synthesized and structurally characterized through a combined approach of FT-ICR and LTQ mass spectrometry. The support of both high-resolution and low-resolution mass spectrometric data namely accurate mass measurements, isotopic distribu-tion and MSn spectra, was crucial to confirm the success of the synthesis. These compounds were further evaluated for inhibitory activity against a total of twenty-nine Gram-positive and Gram-negative bacteria to determine the action spectrum and the antimicrobial effectiveness. Results demonstrated compounds’ antimicrobial activity against many tested bacterial species, providing an inhibitory effect linked to different chemical structure and suggesting that the new-synthesized derivatives could be considered as promising antimicrobial agents.

A new method for the synthesis of azido-propargyloxy derivatives of 1,3,5-triazine has been developed. The antibacterial activity against E. coli bacteria of propargyloxy substituted 1,3,5-triazines - 2,4,6-trispropargyloxy-1,3,5-triazine, 2-azido-4,6-bispropargyloxy-1,3,5-triazine and 2,4-diazido-6-propargyloxy-1,3,5-triazine and their hyperbranched polymers. It has been shown that the presence of an azide group in the compound directly affects the antibacterial activity. The cytotoxicity of these compounds against the M-HeLa, FetMSC and Vero cell lines was studied. The IC50 value was determined for low molecular weight compounds. It has been shown that hyperbranched polymers without azide groups don’t exhibit pronounced cytotoxicity and can be used in biomedical applications.

This comprehensive scientific review provides an in-depth analysis of both the natural compounds, pyrethrins, and their synthetic derivatives, pyrethroids, focusing on their classification, biosynthesis, mechanism of action, general and pharmaceutical uses, as well as their toxicity and environmental impact. Pyrethrins, derived from certain plant species, have long been recognized for their potent insecticidal properties. The review begins by examining the classification of pyrethrins and pyrethroids, elucidating their structural characteristics and unique features within the field of natural and synthetic compounds. The biosynthetic pathways responsible for producing pyrethrins in plants are discussed, highlighting the enzymatic reactions and genetic regulation involved. In addition, the synthesis of pyrethroid derivatives is explored, including both natural and synthetic sources and potential optimization strategies. Understanding the mechanisms of action by which pyrethrins and pyrethroids exert their insecticidal effects is a crucial aspect of this review. Complex interactions with the nervous systems of target organisms are examined, providing insights into their selective toxicity and modes of action. In addition, the various applications of these compounds are explored, from their use in agriculture for pest control to their incorporation into household insecticides and potential pharmaceutical applications. The review also critically evaluates the potential toxicity of pyrethrins and pyrethroids to human health. By consolidating current knowledge and research findings, this review provides a comprehensive understanding of the properties and applications of pyrethrins and pyrethroids, highlighting their benefits and risks, and the importance of responsible and sustainable use in various areas.

Tuberculosis (TB) is a leading infectious disease with serious antibiotic resistance. The benzothiazinone (BTZ) scaffold PBTZ169, an inhibitor of the decaprenylphosphoryl-β-D-ribose 2'-oxidase (DprE1) in Mycobacterium tuberculosis (Mtb), showed anti-TB potential in animal model and piloted clinical tests. Although highly potent, the BTZ type DprE1 inhibitors in general shows extremely low aqueous solubility, which adversely affect the drug like property. To improve the compounds physiochemical properties, we generated a series of BTZ analogues. Several optimized compounds had MIC values against Mtb in single digit nanomolar. The representative compound 37 displayed improved solubility and bioavailability compared to the lead compound. Additionally, compound 37 shows Mtb-killing ability in an acute infection mouse model.

Cutaneous leishmaniasis (CL) is a neglected tropical disease, which causes severe skin lesions. Due to the lack of effective vaccines, and toxicity or reduced effectiveness of available drugs in addition to complex and prolonged treatments, there is an urgent need to develop alternatives for the treatment for CL with different mechanisms of action. In our effort to search for new promising hits against Leishmania parasites we prepared 18 acyl hydrazone derivatives of thiochroman-4-ones. Compounds were evaluated for their in vitro antileishmanial activity against the intracellular amastigote form of Leishmania panamensis and cytotoxic activity against human monocytes (U-937 ATCC CRL-1593.2). Our results show that derivatization of the thiochroman-4-ones with acyl hydrazones significantly enhances the antileishmanial activity. Among the compounds tested semicarbazone and thiosemicarbazone derivatives of thioflavanone 19 and 20 displayed the highest antileishmanial activities, with EC₅₀ values of 5.4 and 5.1 µM and low cytotoxicities (100.2 and 50.1 µM respectively), resulting in higher indexes of selectivity (IS).

The fungus Xylaria sp. Z184, harvested from the leaves of Fallopia convolvulus (L.) Á. Löve, has been isolated for the first time. Chemical investigation of the methanol extract of this strain’s culture broth led to the discovery of three new pyranone derivatives fallopiaxylaresters A-C (1–3) and a new bisabolane-type sesquiterpenoid named fallopiaxylarol A (4), along with the first complete set of spectroscopic data for the previously-reported pestalotiopyrone M (5). Known pyranone derivatives (6–11), sesquiterpenoids (12–14), isocoumarin derivatives (15–17), and an aromatic allenic ether (18) were co-isolated. Their structures were elucidated by the interpretation of HRESIMS, 1D, 2D NMR spectroscopy and quantum chemical computation method. The antimicrobial, anti-inflammatory, and α-glucosidase inhibitory activities of selected compounds and crude extract were evaluated in vitro. The extract inhibited nitric oxide (NO) production induced by lipopolysaccharide (LPS) in murine RAW264.7 macrophage cells, with an inhibition rate of 77.28 ± 0.82% at a concentration of 50 μg/mL. The compounds 5, 7 and 8 displayed weak antibacterial activity against Staphylococcus areus subsp. aureus at a concentration of 100 μM.

Ferulic acid has numerous beneficial effects for human health, which are frequently attributed to its antioxidant behavior. In this report many of them are reviewed and 185 new ferulic acid derivatives are computationally designed, using the CADMA-Chem protocol. For the later, the chemical space was sampled and evaluated. To that purpose selection and elimination scores were used, which are built from a set of descriptors accounting for ADME properties, toxicity, and synthetic accessibility. After the first screening, 12 derivatives were selected and further investigated. Their potential role as antioxidants was predicted from reactivity indexes, directed related with the formal hydrogen atom transfer and the single electron transfer mechanisms. The best performing molecules were identified by comparisons with the parent molecule and two references: Trolox and alpha-tocopherol. Their potential as polygenic neuroprotectors was investigated through the interactions with enzymes directed related with the etiologies of Parkinson’s and Alzheimer’s diseases. They are acetylcholinesterase, catechol-O-methyltransferase, and monoamine oxidase B. Based on the obtained results, the most promising candidates (FA-26, FA-118, and FA-138) are proposed as multifunctional antioxidants with potential neuroprotective effects. The findings derived from this investigation are encouraging and might promote further investigations on these molecules.

The concerning rise in emergence and prevalence of resistant strains to drugs of M. tuberculosis has ,the prompted researchers to look for new and effective treatments. With this motive, biscoumarins were identified as the lead molecules on a whole-cell-based screening of several less explored low molecular weight bioactive compounds against M. tuberculosis strains. Among the screened biscoumarins, the highest dock score derivatives were synthesized (a-h) using a programmable microwave synthesizer for better yields and reaction control. The synthesized derivatives were evaluated against H37Rv, H37Ra, M. smegmatis, an MDR surrogate model, and other bacterial strains for the structure-activity response. Assessment of the synthesized library against mycobacterial strains led to the identification of compounds (f and d) as lead anti-tuberculosis agents. Compounds (f and d) exhibited less toxicity against human cell lines. At the same time, it displayed enjoyable activity wherein MIC concentrations were observed to be 16- and 32 µg/mL against the susceptible H37Rv, and H37Ra strains of M. tuberculosis and MIC value of 128 µg/mL for M. smegmatis, respectively. For mechanistic insights and identification of drug binding targets, molecular docking and dynamic simulations were employed for a panel of 16 mycobacterial enzymes essential for mycobacterial growth and survival. These in silico studies revealed the DprE1 enzyme as a druggable target for the anti-tuberculosis activity of the selected biscoumarins derivatives. Further investigation is underway in our laboratory, leading to its development as an anti-tuberculosis drug (animal model studies).

Background: When homeostasis is disturbed it can occur a pathological event named inflammation. The main drugs used in the treatment consist of the non-steroidal and steroidal anti-inflammatory drugs. However, the side effects remain an obstacle during the treatments. In this work we aimed to evaluate three new regioisomers analogues of naphthyl-N-acylhydrazone derivatives. Methods: Acute models of inflammation in vivo (formalin-induced licking and carrageenan-induced inflammation) as well as in vitro were used to evaluate the effects of LASSBio-2039, LASSBio-2040, and LASSBio-2041. Results: All three substances (at 1, 10 or 30 µmol/kg) presented significant effect in the in vivo model reducing leukocyte migration, nitric oxide (NO) and interleukin-1β production. It was observed that only LASSBio-2039 significantly reduced cell migration in vitro. None of the LASSBios did affect inducible nitric oxide synthase activity nor presented NO scavenger effect. It was not observed any toxic effect neither in vivo nor in vitro. The new regioisomers analogues of naphthyl-N-acylhydrazone derivatives presented a significant anti-inflammatory activity suggesting LASSBio-2039 with a direct effect in leukocytes migratory capacity. Conclusions: Taken together the data indicate that these substances present promising effect for de development a prototype for new drugs.

Inhibition of acetylcholinesterase (AChE) enzyme is a known procedure to treat severe Alzheimer's disease through increasing the acetylcholine level in the brain and thus slowing down the progression of Alzheimer's symptoms. The approved medications are only considered as palliative and addressed some reported deficiencies. Therefore, the demand for safe and effective compounds is substantially increasing. A newly series of coumaryl 1,3-selenazoles derivatives was synthesized in four steps. Then, their antioxidant activities were evaluated using DPPH, ABTS cation radical scavenging assay and cupric reducing antioxidant capacities (CUPRAC). The anticholinesterase activities were evaluated using the Ellman method. Then, the docking studies were carried out to explain the possible correlation between in vitro anticholinesterase activity results and the ligand-receptor interactions. Ten new coumaryl 1,3-selenazoles (5a-5d series and 6a-6f series) derivatives were successfully synthesized. The DPPH radical scavenging assay showed that all tested compounds have IC50 value > 200 μM, for ABTS cation radical scavenging assay the IC50 value > 1000 μM and for CUPRAC assay the IC50 value > 200 μM. Compound 5c was found to be the most active compound against AChE and BChE in its series with IC50 value for AChE is 99.76 μM and IC50 for BChE is 140.28 μM while 6b exhibited the most potent inhibition in its series with IC50 value for AChE is 56.01 μM and IC50 for BChE is 121.34 μM. Besides, the docking studies showed that compound 5c and 6b formed π-π stacking interaction with aromatic residues at the active site of AChE and BChE, which is responsible for inhibiting the enzymes. This shows that the synthesized compounds contain skeletal structures that can interact and inhibit within the enzymes active site.

Curcumin and trans-cinnamaldehyde are acrolein-based Michael acceptor compounds that are commonly found in domestic condiments, and known to cause cancer cell death via redox mechanisms. Based on the structural features of these compounds we designed and synthesized several 2-cinnamamido-N-substituted-cinnamamide (bis-cinnamamide) compounds. One of the derivatives, (Z)-2-[(E)-cinnamamido]-3-phenyl-N-propylacrylamide 1512 showed a moderate antiproliferative potency (HCT-116 cell line inhibition of 32.0 µM), good selectivity profile (no inhibition of normal cell lines), and proven cellular activities leading to apoptosis. SAR studies led to more than 10-fold increase in activity. Our most promising compound, [(Z)-3-(1H-indol-3-yl)-N-propyl-2-[(E)-3-(thien-2-yl)propenamido)propenamide] 4112 killed colon cancer cells at IC50 = 0.89 µM (Caco-2), 2.85 µM (HCT-116) and 1.65 µM (HT-29), while exhibiting much weaker potency on C-166 and BHK normal cell lines (IC50 = 71 µM and 77.6 µM, respectively). Cellular studies towards identifying the compounds mechanism of cytotoxic activities revealed that apoptotic induction occurs in part as a result of oxidative stress. Importantly, the compounds showed inhibition of cancer stem cells that are critical for maintaining the potential for self-renewal and stemness. The results presented here show discovery of covalently-acting Michael addition compounds that potently kill cancer cells by a defined mechanism, with minimal effect on normal noncancerous cell.

Natural products are an important source of antibacterial agents. Canthin-6-one alkaloids have displayed potential antibacterial activity based on our previous work. In order to improve the activity, twenty-two new 3-N-benzylated 10-methoxy canthin-6-ones were designed and synthesized through quaternization reaction. The in vitro antibacterial activity against three bacteria was evaluated by double dilution method. Four compounds (6f, 6i, 6p and 6t) displayed 2-fold superiority (minimum inhibitory concentration (MIC) = 3.91 µg/mL) against agricultural pathogenic bacteria R. solanacearum and P. syringae than agrochemical propineb. Moreover, the structure–activity relationships (SARs) were also carefully summarized in order to guide the development of antibacterial canthin-6-one agents.

Compounds with tyrosinase inhibitory efficacy could be effective as depigmenting agents. Although a large number of natural and synthetic tyrosinase inhibitors have been reported, few of them are used as skin-whitening agents due to poor activity and safety concerns. 3-(2,4-Dihydroxyphenyl)propionic acid (DPPA), a naturally occurring compound isolated from Ficus carica, was previously discovered as a moderate tyrosinase inhibitor. In this study, the structure-activity relationship study of DPPA was conducted. Compound 3g, with the 2,4-resorcinol subunit and terminal hydrophobic di-butylamino group, was identified with low nanomolar enzymatic IC₅₀ value. Additionally, compound 3g could effectively reduce melanin levels in B16-F10 melanoma cells treated with α-melanocyte-stimulating hormone (α-MSH) without affecting cell viability and proliferation. All these results indicated that compound 3g could be considered as a promising candidate for the treatment of diseases associated with hyperpigmentation.

P-glycoprotein (Pgp) determines resistance to a broad spectrum of drugs in glioblastoma multiforme (GB) because it is highly expressed in GB stem cells and in brain-blood barrier (BBB), the peculiar endothelium surrounding brain. Inhibiting Pgp activity in BBB and GB is still an open challenge. Here, we tested the efficacy of a small library of tetrahydroisoquinoline derivatives with an EC₅₀ for Pgp < 50 nM, in primary human BBB cells and in patients-derived GB, from which we isolated differentiated/adherent cells (AC, i.e. Pgp-negative/doxorubicin-sensitive cells) and stem cells (neurospheres, NS, i.e. Pgp-positive/doxorubicin-resistant cells). At 1 nM, 3 compounds increased the delivery of doxorubicin, a typical substrate of Pgp, across BBB monolayer, without altering expression and activity of other transporters. The compounds increased the drug accumulation within NS, restoring necrosis, apoptosis and reduction in cell viability induced by doxorubicin. In co-culture systems, the compounds added to the luminal face of BBB increased the delivery of doxorubicin to NS growing under BBB and rescued the drug’s cytotoxicity. Our work identified new ligands of Pgp active at low nanomolar concentrations, that effectively reduce Pgp activity in BBB and GB, and can improve chemotherapy efficacy in this tumor.

Lipophilic oligonucleotide derivatives are a potent approach to the intracellular delivery of nucleic acids. The binding of these derivatives to serum albumin is a major determinant of their fate in the body, as its structure contains several sites of high affinity for hydrophobic compounds. This study focuses on the features of self-association and non-covalent interactions with human serum albumin of novel self-penetrating oligonucleotide derivatives. The study revealed that the introduction of a triazinyl phosphoramidate modification bearing two dodecyl groups at the 3' end region of the oligonucleotide sequence has a negligible effect on its affinity for the complementary sequence. Dynamic light scattering verified that the amphiphilic oligonucleotides under study can self-assemble into micelle-like particles ranging from 8 to 15 nm in size. The oligonucleotides with dodecyl groups form stable complexes with human serum albumin with a dissociation constant of approximately 10-6 M. The oligonucleotide micelles are simultaneously destroyed upon binding to albumin. Using an electrophoretic mobility shift assay and affinity modification, we examined the ability of DNA duplexes containing triazinyl phosphoramidate oligonucleotides to interact with Ku antigen and PARP1, as well as the mutual influence of PARP1 and albumin or Ku antigen and albumin upon interaction with DNA duplexes. These findings, together with the capability of dodecyl-containing derivatives to effectively penetrate different cells, such as HEK293 and T98G, indicate that the oligonucleotides under study can be considered as a platform for the development of therapeutic preparations with a target effect.

The -blocker (S)-practolol ((S)-N-(4-(2-hydroxy (isopropylamino)propoxy)phenyl)acetamide) was synthesized with 96% enantiomeric excess (ee) from the chlorohydrin (R)-N-(4-(3-chloro-2 hydroxypropoxy)phenyl)acetamide, which was produced in 97% ee and with 27% yield. Racemic building block 1-((1H-indol-4-yl)oxy)-3-chloropropan-2-ol for the -blocker pindolol was produced in 53% yield and (R)-1-((1H-indol-4-yl)oxy)-3-chloropropan-2-ol was produced in 92% ee. The chlorohydrin 7-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one, a building block for a derivative of carteolol was produced in 77% yield. (R)-7-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one was obtained in 96% ee. The S-enantiomer of this carteolol derivative was produced in 97% ee in 87% yield. Racemic building block 5-(3-chloro-2-hydroxypropoxy)- 3,4-dihydroquinolin-2(1H)-one, building block for the drug carteolol was also produced in 53% yield, with 99% ee of the R-chlorohydrin (R)-5-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one. The yield of all four chlorohydrins increased by use of catalytic amounts of base. The reason for this was found to be less formation of the dimeric by-products compared to use of higher concentration of the base. An overall reduction of reagents and reaction time was also obtained compared to our previous reported data of similar compounds. The enantiomers of the chlorohydrin building blocks were obtained by kinetic resolution of the racemate in transesterification reactions catalyzed by Candida antarctica Lipase B (CALB) from SyncoZymes Co, Shanghai, China. Optical rotations confirmed the absolute configuration of the enantiopure drugs.

Since the discovery of the aggregation-induced emission effect in 2001, diaminodicyanoquinone derivatives (DADQs) have presented interesting fluorescence properties, allowing them to be considered fluorescent dyes capable of showing quantum yields above 90%. Besides, the diaminodiacyanoquinone core represents a versatile building block propense either to modification or integration into different systems to obtain and provide them unique photophysical features. Herein, we carried out a theoretical study on the fluorescence properties of three different diaminodicyanoquinodimethane systems. Therefore, time-dependent density functional theory (TD-DFT) was used to obtain the values associated with the dipole moments, oscillator strengths, and the conformational energies between the ground and the first excited states of each molecule. The results suggest that only two of the three studied systems possess significant luminescent properties. In a further stage, the theoretical insights were confirmed by means of experimental measurements, which not only retrieved the luminescence of the DADQs, but also suggest a preliminary and promising antibacterial activity of these systems.

We present a summary of our protocol for employment of small-molecule circadian rhythm modulators. The abilities of compounds to affect oscillations have received significant attention. We outline assessments of circadian changes using indirubin-3’-oxime (IO), 5-iodo-indirubin-3’-oxime (5I-IO), and 5-sulfonic acid-indirubin-3’-oxime (5SA-IO), analyzing effects on Bmal1 and Per2 oscillations and oncogenic features.

Study of differential equation theory has come a long way with applications in the various fields. In 1961, Zygmund and Calderón introduced the notion of derivatives on metric Lr which proved to be better in applications than approximate derivatives. But most of the studies involved are on fuzzy set theory, so it seems likely that intuitionistic fuzzy Lr - norm - based derivatives deserve study. In the study, the fuzzy derivative is extended to intuitionistic fuzzy derivatives with respect.to Lr - norm - based derivatives using intuitionistic fuzzy number valued functions. The efficacy of the proposed method is established by proving the associated theorems along with numerical examples. Further, the Cauchy problem is also studied with respect to intuitionistic fuzzy setting.

Chronic hepatitis B (CHB) infection and the Hepatitis B virus X protein (HBx) are major risk factors associated with hepatocellular carcinoma (HCC). In CHB infection, HBx induces mitochondrial dysfunction, exhaustion and impaired function in hepatocytes. Restoring hepatocyte health along with reduction in virus replication could be an ideal treatment for CHB. Thiourea derivatives are well known for their antiviral property though their effect on mitochondrial and/ or hepatocyte health remains obscure. This study focus on the repurposing of thiourea derivatives (DSA-00, DSA-02, and DSA-09) on hepatocyte replenishment. HepG2.2.15 cells were treated with thiourea derivatives, alongside Entecavir (ETV). The proteomics analysis showed both DSA-00 and ETV were enriched with proteins associated with antiviral responses. In addition, DSA-00 additionally showed increase in proteins linked to mitochondrial response. Whereas DSA-02 exhibited association with innate immune system and citric acid cycle and DSA-09 displayed pathways similar to DSA-00 and ETV. Treated groups exhibited enhanced bio-energetic and antiviral response as compared to the untreated group. FACS analysis revealed the restoration of exhausted hepatocytes by thiourea derivatives through targeting mitochondria. Our findings suggest that thiourea derivatives hold potential as a novel therapeutic agent that seems to restore mitochondrial health along with anti-viral response in CHB.

The near-infrared (NIR) organic dyes with strong ultrafast nonlinear optical (NLO) activities are of importance for various applications. However, such kinds of dyes are still scarce. In this work, we have compared the NLO properties of two NIR Aza-BODIPY derivatives, in which the strong electron-donating groups, namely 4-(N, N-dimethylamino) phenyl and 1-ethyl-1,2,3,4-tetrahydroquinoline groups, are connected with the cores of Aza-BODIPY. Z-Scan experimental results show that two Aza-BODIPY derivatives exhibit strong saturation absorption and large modulation depth under the excitation of femtosecond pulses at 800 nm. Under 1300 nm excitation, two derivatives exhibit strong nonlinear refraction. In addition, the Aza-BODIPY derivatives also display effective two-photon excited fluorescence emission in the wavelength range of 1200-1600 nm. Based on the experimental results, it is found that 1-ethyl-1,2,3,4-tetrahydroquinoline group can more effectively enhance the NLO properties of Aza-BODIPY derivatives compared with the 4-(N, N-dimethylamino) phenyl group, thus providing new possibilities for the design and development of NIR NLO materials.

In this paper, the 1st level general fractional derivatives of arbitrary order are defined and investigated for the first time. We start with a generalization of the Sonin condition for the kernels of the general fractional integrals and derivatives and then specify a set of the kernels that satisfy this condition and posses an integrable singularity of power law type at the origin. The 1st level general fractional derivatives of arbitrary order are integro-differential operators of convolution type with the kernels from this set. They contain both the general fractional derivatives of arbitrary order of the Riemann-Liouville type and the regularized general fractional derivatives of arbitrary order considered in the literature so far. For the 1st level general fractional derivatives of arbitrary order, some important properties including the 1st and the 2nd fundamental theorems of Fractional Calculus are formulated and proved.

Cisplatin (CDDP), carboplatin (CP), and oxaliplatin (OXP) are three platinating agents clinically approved worldwide for use against a variety of cancers. They are canonically known as DNA damage inducers; however, that is only one of their mechanisms of cytotoxicity. CDDP mediates its effects through DNA damage-induced transcription inhibition and apoptotic signalling. In addition, CDDP targets the endoplasmic reticulum (ER) to induce ER-stress, the mitochondria via mitochondrial DNA damage leading to ROS production, and the plasma membrane and cytoskeletal components. CP acts in a similar fashion to CDDP by inducing DNA damage, mitochondrial damage, and ER stress. Additionally, CP is also able to upregulate micro-RNA activity, enhancing intrinsic apoptosis. OXP, on the other hand, at first induces damage to all the same targets as CDDP and CP, yet it is also capable of inducing immunogenic cell death via ER stress and can decrease ribosome biogenesis through its nucleolar effects. In this comprehensive review, we provide detailed mechanisms of action for the three platinating agents, going beyond their nuclear effects to include their cytoplasmic impact within cancer cells. In addition, we cover their current clinical use and limitations, including side effects and mechanisms of resistance.

The numerous biological activities of phenothiazine and sulphonamide derivatives, especially their antibacterial qualities, have attracted so much interest. In this study, the synthesis and characterization of phenothiazine-3-sulphonamide derivatives and evaluation their antimicrobial activity against the following pathogenic microorganisms is reported. Two gram-positive bacteria; (Staphylococcus aureus, and Streptococcus pyogenes), two gram-negative bacteria; (Escherichia coli, and Salmonella typhi) as well as one fungus (Aspergillus fumigatus) were used while ciprofloxacin, gentamycin and ketoconazole served as standard drugs. The synthesis of the derivatives was achieved through a base catalyzed the reaction of 4-chloroaniline with 1-naphthylamine to form 1-(naphthalen-1-yl) benzene-1,4-diamine. This intermediate was then treated with sulphur and iodine to yield the phenothiazine derivative while subsequent treatment of the phenothiazine compound with sulphonyl chlorides gave the final products. The synthesized compounds were characterized via proton nuclear magnetic resonance (1HNMR), carbon-13 nuclear magnetic resonance (13C NMR) and Fourier-transform infrared (FTIR) spectroscopic techniques. The minimum inhibitory concentration (MIC) of each compound was then determined using the agar well diffusion method. To predict the binding energies and patterns of the synthesized compounds with target proteins of the above mentioned microorganisms, molecular docking simulations were run using Autodock Vina software (version 4.2). The spectra data of the compounds for FTIR, 1H NMR and 13C NMR (δ) spectral data were consistent with the assigned structures of the synthesized compounds. The binding energies (kcal/mol) for in silico antimicrobial studies were in the range -5.1 to -7.6 kcal/mol. The MIC values were in the range -3.5 to 1.0 mg/L. The results of the in vitro test revealed that the synthesized compounds exhibits promising antimicrobial activity, and showed excellent bactericidal and fungicidal activities. The results obtained showed that the synthesized compounds possess drug-like properties and are good starting materials for drug production.

Sirtuins are a family of Class III epigenetic modifying enzymes involved in regulating cellular processes through the removal of acetyl groups from proteins. They rely on NAD+ as a coenzyme in contrast with classical HDACs (Class I, II, and IV) that depends on Zn+ for their activation, linking their function to cellular energy levels. There are seven mammalian sirtuin isoforms (SIRT1-7), each located in different subcellular compartments. Sirtuins act as master regulators of cellular homeostasis, responding to changes in nutrient availability and energy status. They play vital roles in diverse physiological and pathological conditions, making them promising therapeutic targets for various diseases, including cancer, neurodegenerative disorders, and metabolic diseases. High levels of SIRT6 are involved in the cancer progression of many tumor types and our previous studies revealed that sirtuin 6 was highly expressed in NSCLC cells and its inhibition potentially favored apoptosis and cell cycle arrest. Sirt6 emerged as a promising target and inhibitors of natural and synthetic sources are highly warranted. Imidazole derivatives are often investigated as sirtuin regulators due to their ability to interact with the binding site and modulate their activity. Imidazole bestows many possible substitutions on its ring and neighboring atoms, to design and synthesize derivatives with specific target selectivity and improved pharmacokinetic properties, optimizing drug development. We recently developed imidazole-based derivatives that potentially inhibited classical HDAC enzymes. Therefore, we evaluated the Sirtuin inhibition activity of our in-house compound comprised of imidazole derivatives and the strongest inhibition was observed with Ethyl 2-[5-(4-chlorophenyl)-2-methyl-1-H-Imidazole-4-yl) acetate against Sirt6 by in-silico and protein expression studies. Our results suggested that Ethyl 2-[5-(4-chlorophenyl)-2-methyl-1-H-Imidazole-4-yl) acetate could be a potential novel sirt6 inhibitor.

Ants of the genus Solenopsis are important invasive pests in the world. Due to their high dispersion capacity, aggressive behavior and because they feed on various sources of vegetable and animal protein, these insects have caused serious damage to public health and agriculture. The control has usually been carried out through the use of organosynthetic insecticides. However, due to the ecological and environmental impacts caused by the use these products, more sustainable alternatives have been sought for their control. Faced with these problems and due to the scarcity of registered products for the control of these insects, we aimed with this study to synthesize and evaluate the anticidal potential of carvacrol derivatives. The lethal and sublethal effects caused by these derivatives were compared with the essential oil of Lippia gracilis (50.7% carvacrol) and with the base molecule — carvacrol. Carvacryl benzoate was the most toxic derivative to Solenopsis sp. with an LD50 of 3.20 g/ mg. This compound was about 2 and 7.6 times, more toxic than carvacrol at the doses needed to kill 50 and 90% of populations, respectively. The workers of Solenopsis sp. showed a rapid reduction in survival when exposed to carvacrol (LT50 = 8.43h) and carvacryl benzoate (LT50 = 8.87h). Insects treated with sublethal doses of the compounds did not show significant effects on self-cleaning, allogrooming and aggregation, with the exception of those treated with L. gracilis essential oil. The oil increased self-cleaning and reduced allogrooming and aggregation. Ants treated with carvacrol and carvacryl benzoate showed greater distance and speed when compared to the control. These compounds decreased meanders and angular velocity. When live workers were exposed to dead individuals at the LD90 of the compounds, carvacryl benzoate was the derivative that most reduced insects survival, due to horizontal transfer. These results show the potential of the carvacrol derivative — carvacryl benzoate — for the alternative management of ants of the genus Solenopsis sp.

Cereals and their derivatives are the basis of human nutrition. However, cereals also contribute to the dietary exposure to toxic metals that may pose a risk. Strengthening food security and nutrition information is a high priority challenge for the Cape Verde Government. The toxic metals content (Cr, Ni, Sr, Al, Cd, Pb) has been determined in 126 samples of cereals and derivatives (rice, corn gofio, corn flour, wheat flour, corn, wheat) consumed in Cape Verde. Wheat flour samples stand out for registering the highest Sr (1.60 mg/kg), Ni (0.25 mg/kg) and Cr (0.13 mg/kg). The results show relevant Al levels (1.17 – 13.4 mg/kg) with its highest levels in corn gofio. The mean Pb average content in the cereals is 0.03 – 0.08 mg/kg with the highest level observed in corn gofio. The Al and Pb levels are lower in cereals without husks. A consumption of 100 g/day of corn gofio provide an intake of 1.34 mg Al/day (13.7% of the tolerable weekly intake established at 1 mg/kg bw/week) and 8 µg Pb/day (20% of the BMDL set at 0.63 µg/kg bw/day for nephrotoxic effects). The minimization of the dietary exposure of the Cape Verdean population to toxic metals is through the importation of higher quality cereals.

A variety of myricetin derivatives bearing ferulic acid amide scaffolds were designed and synthesized. The structures of all title compounds were determined by 1 H NMR, 13 C NMR, 19 F NMR and HRMS. Preliminary bioassays suggested that some of the target compounds exhibited remarkable antiviral activities. In particular, compound 4l possessed significant protection activity against tobacco mosaic virus (TMV), with an half maximal effective concentration (EC50) value of 196.11 μg/mL, which was better than commercial agent ningnamycin (447.92 μg/mL). Meanwhile, microscale thermophoresis (MST) indicated that compound 4l have strong binding capability to tobacco mosaic virus coat protein (TMV-CP) with dissociation constant (Kd) values of 0.34 μmol/L, which was better than ningnamycin (0.52 μmol/L). These results suggest that novel myricetin derivatives bearing ferulic acid amide scaffolds may be considered as an activator for antiviral agents.

We have synthesized quinoxaline analogs (1-25), characterized by 1HNMR and HREI-MS and evaluated for thymidine phosphorylase inhibition. Among the series, nineteen analogs showed better inhibition when compared with the standard inhibitor 7-Deazaxanthine (IC50 = 38.68 ± 4.42 µM). The most potent analog among the series is analog 25 with IC50 value 3.20 ± 0.10 µM. Sixteen analogs 1, 2, 3, 4, 5, 6, 7, 12, 13, 14, 15, 16, 17, 18, 21and 24 showed outstanding inhibition which is many folds better than the standard 7-Deazaxanthine. Two analogs 8 and 9 showed moderate inhibition. A structure- activity relationship has been established mainly based upon the substitution pattern on the phenyl ring. The binding interactions of the active compounds were confirmed through molecular docking studies.