Spiropyrrolidine/spiroindolizino[6,7-b]indole heterocyclic hybrids: Stereoselective synthesis, cholinesterase inhibitory activity and their molecular docking study

Abstract

A regio and stereo- selective synthesis of hitherto unexplored hybrid heterocyclic system comprising spiropyrrolidine, indolizino[6,7-b]indole units in good to excellent yields, has been developed via three component 1,3-dipolar cycloaddition and concomitant trifluoroacetic acid catalyzed Pictet-Spengler cyclization with paraformaldehyde. The newly synthesized compounds were evaluated for their in vitro acetylcholinesterase (AChE) and butylcholinesterase (BChE) enzyme inhibitory activities. Most of the synthesized compounds showed good inhibitory activity, among them, compounds 4d and 4g displayed highest potency against AChE (IC50 1.88 and 1.98 μM), and BChE (IC50 18.32 and 10.21 μM) enzyme, respectively than the standard drug, galanthamine. Molecular modeling simulation was investigated for the most active compounds 4d and 4g on AChE and BChE enzymes to disclose the binding and orientation of these molecules into active site of respective receptors.