Synthesis, biological evaluation and in silico study of 4-(benzo[d]thiazole-2-yl) phenols based on 4-hydroxy coumarin as acetylcholinesterase inhibitors.

Alzheimer's disease, characterized by cognitive decline and memory loss, is associated with decreased acetylcholine levels due to acetylcholinesterase (AChE) activity. Compounds containing a coumarin heterocyclic core coupled with thiazole exhibit excellent acetylcholinesterase inhibitory activity. In this work, we designed and synthesized a series of 4-(benzo[d]thiazole-2-yl) phenols based on 4-hydroxycoumarin. The compounds were synthesized and their inhibitory activities were evaluated through in vitro biological assays. Of the compounds investigated, 3i exhibited the strongest inhibitory activity, with an IC50 value of 2.7 µM. Molecular docking and molecular dynamics simulations were employed to elucidate the binding interactions and stability of the synthesized compounds with AChE. The results demonstrated promising inhibitory activity, suggesting potential therapeutic applications for Alzheimer's disease. This research contributes to the development of coumarin-based heterocyclic compounds as effective AChE inhibitors.