A facile ionic liquid promoted synthesis, cholinesterase inhibitory activity and molecular modeling study of novel highly functionalized spiropyrrolidines

Abdulrahman I Almansour; Raju Suresh Kumar; Natarajan Arumugam; Alireza Basiri; Yalda Kia; Mohamed Ashraf Ali; Mehvish Farooq; Vikneswaran Murugaiyah

doi:10.3390/molecules20022296

A facile ionic liquid promoted synthesis, cholinesterase inhibitory activity and molecular modeling study of novel highly functionalized spiropyrrolidines

Molecules. 2015 Jan 29;20(2):2296-309. doi: 10.3390/molecules20022296.

Authors

Abdulrahman I Almansour¹, Raju Suresh Kumar², Natarajan Arumugam³, Alireza Basiri⁴, Yalda Kia⁵, Mohamed Ashraf Ali⁶, Mehvish Farooq⁷, Vikneswaran Murugaiyah⁸

Affiliations

¹ Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. almansor@ksu.edu.sa.
² Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. sraju@ksu.edu.sa.
³ Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. aruorgchem@gmail.com.
⁴ School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800, Malaysia. diba115920@gmail.com.
⁵ School of Chemical Sciences, Universiti Sains Malaysia, Minden 11800, Malaysia. kia.yalda@yahoo.com.
⁶ Pharmacogenetic and Novel Therapeutic Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden 11800, Malaysia. asraf80med@yahoo.com.
⁷ Institute of Pharmaceutical Science, King's College London, London SE1 9NH, UK. Mehvish.farooq@kcl.ac.uk.
⁸ School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800, Malaysia. vicky@usm.my.

Abstract

A series of novel dimethoxyindanone embedded spiropyrrolidines were synthesized in ionic liquid, [bmim]Br and were evaluated for their inhibitory activities towards cholinesterases. Among the spiropyrrolidines, compound 4f exhibited the most potent activity with an IC50 value of 1.57 µM against acethylcholinesterase (AChE). Molecular docking simulation for the most active compound was employed with the aim of disclosing its binding mechanism to the active site of AChE receptor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylcholinesterase / chemistry
Catalytic Domain
Cholinesterase Inhibitors / chemical synthesis*
Cycloaddition Reaction
Ionic Liquids / chemistry
Models, Molecular
Molecular Docking Simulation
Pyrrolidines / chemical synthesis*
Spiro Compounds / chemical synthesis*

Substances

Cholinesterase Inhibitors
Ionic Liquids
Pyrrolidines
Spiro Compounds
Acetylcholinesterase