Design, Synthesis, and Biological Evaluation of Some Benzothiazolone Derivatives as Cholinesterase Inhibitors

Abstract In this study, nine new benzothiazolone derivatives ( 6 a – i ) were designed and synthesized to identify potent cholinesterase inhibitors. The compounds were tested in vitro against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) and found to be selective to BChE. Compound 6 f proved the most potent derivative (IC 50 =12.25±0.23 μM) against BChE and was identified as a mixed‐type inhibitor with a K i value of 4.45±0.35 μM according to the kinetic studies. Molecular modelling suggested that the derivatives were druglike and non‐PAINS. Compound 6 f showed good fit in BChE active site interacting with the key sites important for enzyme activity according to the molecular docking study.