Version 1
: Received: 10 October 2023 / Approved: 11 October 2023 / Online: 12 October 2023 (07:10:46 CEST)
How to cite:
Ahmed, A. A.; Babikir, R. R.; Hassan, T. A.; Mohamed Ahmed, A. A.; Taha, L. I.; Elkheir, L. Y. M.; Shantier, S. W.; Ismail, E. M. O. African Natural Products for Multitarget-Based Treatment of Alzheimer’s Disease: An In Silico Study. Preprints2023, 2023100783. https://doi.org/10.20944/preprints202310.0783.v1
Ahmed, A. A.; Babikir, R. R.; Hassan, T. A.; Mohamed Ahmed, A. A.; Taha, L. I.; Elkheir, L. Y. M.; Shantier, S. W.; Ismail, E. M. O. African Natural Products for Multitarget-Based Treatment of Alzheimer’s Disease: An In Silico Study. Preprints 2023, 2023100783. https://doi.org/10.20944/preprints202310.0783.v1
Ahmed, A. A.; Babikir, R. R.; Hassan, T. A.; Mohamed Ahmed, A. A.; Taha, L. I.; Elkheir, L. Y. M.; Shantier, S. W.; Ismail, E. M. O. African Natural Products for Multitarget-Based Treatment of Alzheimer’s Disease: An In Silico Study. Preprints2023, 2023100783. https://doi.org/10.20944/preprints202310.0783.v1
APA Style
Ahmed, A. A., Babikir, R. R., Hassan, T. A., Mohamed Ahmed, A. A., Taha, L. I., Elkheir, L. Y. M., Shantier, S. W., & Ismail, E. M. O. (2023). African Natural Products for Multitarget-Based Treatment of Alzheimer’s Disease: An In Silico Study. Preprints. https://doi.org/10.20944/preprints202310.0783.v1
Chicago/Turabian Style
Ahmed, A. A., Shaza Wagiealla Shantier and Esraa Mohamed Osman Ismail. 2023 "African Natural Products for Multitarget-Based Treatment of Alzheimer’s Disease: An In Silico Study" Preprints. https://doi.org/10.20944/preprints202310.0783.v1
Abstract
Alzheimer's disease is a multifactorial neurodegenerative disorder, with Acetylcholinesterase, Butyrylcholinesterase, Beta secretase, Glycogen Synthase Kinase beta and Monoamine oxidase B playing central role in it's pathogenesis.
Therefore, this research aims to discover potential curative multitarget drugs derived from African natural products capable of addressing the multifactorial characteristics of the disease.
In silico approaches were used to filter a 880 african natural compounds library based on selected pharmacokinetic properties. Molecular docking against the five aforementioned proteins, followed by Molecular Mechanics with Generalised Born and Surface Area Solvation scoring for the top compounds were used to assess binding. Density Functional Theory studies were used to assess electronic transitions.
Pharmacokinetic filters resulted in 200 compounds, of which only five were selected after molecular docking. Density Functional Theory and Molecular Mechanics with Generalised Born and Surface Area Solvation scoring resulted in 3 potential multitarget compounds. Compound 157 (ZINC000095485950) showed triple-target inhibitory activity against Butyrylcholinesterase, Glycogen Synthase Kinase beta and Beta-secretase, while compounds 159 (ZINC000095485952) and 696 (ZINC000039144622) showed dual-target inhibitory activity against Butyrylcholinesterase and Glycogen Synthase Kinase beta. Molecular dynamics simulation and further experimental assessments are suggested.
Chemistry and Materials Science, Medicinal Chemistry
Copyright:
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