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

Abstract

AbstractIn 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 (IC50=12.25±0.23 μM) against BChE and was identified as a mixed‐type inhibitor with a Ki 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.