Identification of 1,2,4‐Triazolylthioethanone Scaffold for the Design of New Acetylcholinesterase Inhibitors

Abstract Acetylcholinesterase (AChE) inhibitors are the most effective drugs for Alzheimer's disease treatment. However, considering the potential and failure rates of AChE inhibitors, chemical scaffolds targeting cholinesterase specifically are still very limited. Herein, we report a new class of AChE inhibitors identified by employing a virtual screening approach that combines shape similarity with molecular docking calculations. Virtual screening followed by the evaluation of AChE inhibitory activity allowed us to identify 1,2,4‐triazolylthioethanones as a novel class of AChE inhibitors. Thirteen compounds with 1,2,4‐triazolylthiothanone core and IC 50 values in the range of 0.15±0.07 to 3.32±0.92 μM have been reported here. Our findings shed light into a class of AChE inhibitors that could be useful starting point for the development of novel therapeutics to tackle Alzheimer's disease.