Synthesis, biological evaluation, molecular docking and dynamic simulation of novel benzofuran derivatives as potential agents against Alzheimer's disease

• Published in: Journal of Molecular Structure
• Main Author: Nadeem M.S.; Hayat S.; Rahim F.; Khan J.A.; Ullah H.; Taha M.; Gupta G.; Wadood A.; Shah S.A.A.; Kazmi I.; Iftikhar S.; Muhammad K.
• Format: Article
• Language: English
• Published: Elsevier B.V. 2025
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85206074124&doi=10.1016%2fj.molstruc.2024.140279&partnerID=40&md5=e40ae289255301808cdeec9a7a82529e

We have synthesized novel benzofuran derivatives (1–20), characterized through different spectroscopic techniques such as 1HNMR, 13CNMR, HREI-MS and screened against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. All derivatives showed inhibitory activities having IC50 values ranging from 0.70 ± 0.01 to 28.10 ± 0.50 µM (against AChE), while 0.80 ± 0.01 to 31.20 ± 0.60 µM (against BuChE) as compared to the standard drug Donepezil (IC50 = 2.16 ± 0.12 and 4.50 ± 0.10 µM, respectively). Except derivative 5, all other derivatives of the series showed good inhibitory activity against both acetylcholinesterase and butyrylcholinesterase, but some analogues like 2, 4, 7, 14, 15, and 16 displayed many folds better inhibitory activity than the standard drug donepezil. The influences of substituents on inhibitory activity were superficially resonated via the structure-activity relationship. We established molecular docking and MD simulation studies to confirm the binding interaction between potent derivatives and active sites of enzymes. © 2024 Elsevier B.V.