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

Highly 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), alpha-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 (K(i)s: 2.33-13.81 mu M), BChE (K(i)s: 1.45-12.27 mu M), alpha-glycosidase (K(i)s: 8.03-23.05 mu M), hCA I (K(i)s: 2.23-17.35 mu M) and hCA II (K(i)s: 2.86-18.13 mu M). 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.