Cholinesterase inhibitory activity of highly functionalized fluorinated spiropyrrolidine heterocyclic hybrids

Raju Suresh Kumar; Abdulrahman I Almansour; Natarajan Arumugam; D Kotresha; Thota Sai Manohar; S Venketesh

doi:10.1016/j.sjbs.2020.11.005

Cholinesterase inhibitory activity of highly functionalized fluorinated spiropyrrolidine heterocyclic hybrids

Saudi J Biol Sci. 2021 Jan;28(1):754-761. doi: 10.1016/j.sjbs.2020.11.005. Epub 2020 Nov 11.

Authors

Raju Suresh Kumar¹, Abdulrahman I Almansour¹, Natarajan Arumugam¹, D Kotresha², Thota Sai Manohar³, S Venketesh³

Affiliations

¹ Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
² Department of Studies in Botany, Davangere University, Shivagangothri, Davangere 577007, Karnataka, India.
³ Department of Biosciences, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam, A.P 515 134, India.

Abstract

Two series of dimethoxyindanone imbedded novel fluorinated spiropyrrolidine heterocyclic hybrids were synthesized employing two different less explored azomethine ylides and were measured for their efficiency as inhibitors for Alzheimer's disease. Among the spiropyrrolidine heterocyclic hybrids, the indole based fluorinated compound with a methoxy substituent at the meta- position of the aryl ring exhibited the utmost potent AChE and BChE inhibitory activities with an IC₅₀ of 1.97 ± 0.19 µM and 7.08 ± 0.20 µM respectively. The plausible mechanism of inhibition on ChE receptors was unveiled via molecular docking studies.

Keywords: AChE; Alzheimer’s disease; BChE; Cholinesterase inhibitory activity; Fluorinated spiroheterocyclic hybrids; Molecular docking simulation.