Synthesis and molecular modeling studies of cholinesterase inhibitor dispiro[indoline-3,2′-pyrrolidine-3′,3′′-pyrrolidines]

Abstract

A set of dispiro[indoline-3,2′-pyrrolidine-3′,3′′-pyrrolidines]8a-lwas regioselectively synthesized utilizing multi-component azomethine cycloaddition reaction of 3-(arylmethylidene)pyrrolidine-2,5-diones5a-e, isatins6a-cand sarcosine7. Single crystal X-ray studies of8cadd conclusive support for the structure. Compounds8eand8greveal cholinesterase inhibitory properties with promising efficacy against both AChE and BChE and were found to be more selective towards AChE than BChE as indicted by the selectivity index like Donepezil (a clinically used cholinesterase inhibitory drug). Molecular modeling studies assist in understanding the bio-observations and identifying the responsible parameters behind biological properties.