Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

African Natural Products for Multitarget-Based Treatment of Alzheimer’s Disease: An In Silico Study

Alkhansa Altaher Ahmed
ORCID logo ,
Rawan Ridha Babikir
ORCID logo ,
Tarteel Abdelaal Hassan
,
Asmaa Abdelmonim Mohamed Ahmed
,
Leena Izzeldin Taha
ORCID logo ,
Lamis Yahia Mohamed Elkheir
,
Shaza Wagiealla Shantier
* ,
Esraa Mohamed Osman Ismail
*
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. 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. Preprints 2023, 2023100783. 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.

Keywords

Alzheimer's disease, African natural compounds, Multitarget-directed ligands, AChE, BACE1, BuChE, GSK-3β, MAO-B.

Subject

Chemistry and Materials Science, Medicinal Chemistry

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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