Title: Exploring the molecular structural requirements of Withania somnifera (Ashwagandha) as human acetylcholinesterase inhibitors using molecular modelling studies

Authors: Uttam A. More; Shruti Damania; Parth Desai; Vishalsinh Chauhan; Drashti Dhaduk; Kashish Desai; Malleshappa N. Noolvi

Addresses: Department of Pharmaceutical Chemistry, Shree Dhanvantary Pharmacy College, Kim-394110, Surat, Gujarat, India ' Department of Pharmaceutical Chemistry, Shree Dhanvantary Pharmacy College, Kim-394110, Surat, Gujarat, India ' Department of Pharmaceutical Chemistry, Shree Dhanvantary Pharmacy College, Kim-394110, Surat, Gujarat, India ' Department of Pharmaceutical Chemistry, Shree Dhanvantary Pharmacy College, Kim-394110, Surat, Gujarat, India ' Department of Pharmaceutical Chemistry, Shree Dhanvantary Pharmacy College, Kim-394110, Surat, Gujarat, India ' Department of Pharmaceutical Chemistry, Shree Dhanvantary Pharmacy College, Kim-394110, Surat, Gujarat, India ' Department of Pharmaceutical Chemistry, Shree Dhanvantary Pharmacy College, Kim-394110, Surat, Gujarat, India

Abstract: The naturally obtained Withania somnifera (Ashwagandha) also known as Indian Ginseng have gained a lot of interest as potential Alzheimer's therapy candidates because of their neuroprotection, anti-oxidant, immune boosting, memory power enhancing ability, anti-inflammatory and anti-stress properties. However, more research is required to learn more about the specific mechanisms by which phyto-compounds from Withania somnifera may have neuroprotective effects in Alzheimer's disease. According to our research, these phyto-compounds of Withania somnifera like Pubesenolide, Acetyl Withaferin A and Withanolide L is showing medium blood brain barrier level. The molecular docking study revealed that phyto-compounds ofWithania somnifera are binding with AChE CAS site amino acids Gln71, Trp86, Asn87, Tyr124, His447, PAS site amino acid Tyr72, Tyr341, Trp286, and mid gorge amino acid Arg296, Phe297, Phe338. The findings support the use of phytocompounds of Withania somnifera as a small ligand molecule in the treatment and prevention of Alzheimer's disease pathologies.

Keywords: Withania somnifera; AChE inhibitors; molecular docking; ADMET; anti-Alzheimer agents.

DOI: 10.1504/IJCBDD.2022.128237

International Journal of Computational Biology and Drug Design, 2022 Vol.15 No.3, pp.172 - 194

Received: 28 Jun 2022
Accepted: 19 Jul 2022
Published online: 12 Jan 2023 *

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