Metal‐Free Synthesis via Intramolecular Cyclization, Enzyme Inhibition Properties and Molecular Docking of Novel Isoindolinones

Abstract

AbstractHighly effective one‐pot synthesis of novel isoindolinones from various 2‐benzoylbenzoic acid derivatives with intramolecular cyclization in the presence of chlorosulfonyl isocyanate was reported in mild conditions in the absence a metal catalyst. Novel synthesized compounds were tested against some metabolic enzymes including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α‐glycosidase and carbonic anhydrase I and II (hCA I and hCA II) enzymes that associated with Alzheimer's disease (AD), type‐2 diabetes mellitus (T2DM), epilepsy, and glaucoma. A series of novel isoindolinones (2 a–l) were evaluated as highly potent inhibition ability toward AChE (Kis: 2.33–13.81 μM), BChE (Kis: 1.45–12.27 μM), α‐glycosidase (Kis: 8.03–23.05 μM), hCA I (Kis: 2.23–17.35 μM) and hCA II (Kis: 2.86–18.13 μM). Also, for these inhibitors, in silico molecular docking simulations and calculations were done with the Autodock Vina program to support the in vitro experimental studies.