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

摘要

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),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(2a-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.