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Thirteen benzothiazolone derivatives (M1–M13) were synthesized and evaluated for their inhibitory activity against cholinesterases (ChEs) and monoamine oxidases (MAOs). All the compounds inhibited ChEs more effectively than MAOs. In addition, most of the compounds showed higher inhibitory activities against butyrylcholinesterase (BChE) than acetylcholinesterase (AChE). Compound M13 most potently inhibited BChE with an IC50 value of 1.21 μM, followed by M2 (IC50 = 1.38 μM). Compound M2 had a higher selectivity index (SI) value for BChE over AChE (28.99) than M13 (4.16). The 6-methoxy indole group of M13 was expected to have a greater effect on BChE inhibitory activity than the other groups. Kinetics and reversibility tests showed that M13 was a reversible noncompetitive BChE inhibitor with a Ki value of 1.14 ± 0.21 μM. In a docking simulation, M13 is predicted to form a hydrogen bond with the backbone carbonyl group of Ser287 of BChE through its methoxy indole moiety and π−π interactions between its benzothiazolone group and the side chain of Trp82 with the five-membered pyrrole ring and with the six-membered benzene ring. From these results, it is suggested that M13 is a BChE inhibitor and a potential candidate agent for the treatment of Alzheimer’s disease. © 2022 by the authors. |
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