Ionic liquid-enabled synthesis, cholinesterase inhibitory activity, and molecular docking study of highly functionalized tetrasubstituted pyrrolidines

Raju Suresh Kumar; Abdulrahman I Almansour; Natarajan Arumugam; Dhaifeallah Mohammed Qaide Althomili; Mohammed Altaf; Alireza Basiri; Kotresha D; Thota Sai Manohar; Venketesh S

doi:10.1016/j.bioorg.2018.01.019

Ionic liquid-enabled synthesis, cholinesterase inhibitory activity, and molecular docking study of highly functionalized tetrasubstituted pyrrolidines

Bioorg Chem. 2018 Apr:77:263-268. doi: 10.1016/j.bioorg.2018.01.019. Epub 2018 Feb 3.

Authors

Raju Suresh Kumar¹, Abdulrahman I Almansour², Natarajan Arumugam², Dhaifeallah Mohammed Qaide Althomili², Mohammed Altaf³, Alireza Basiri⁴, Kotresha D⁵, Thota Sai Manohar⁶, Venketesh S⁶

Affiliations

¹ Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. Electronic address: sraju@ksu.edu.sa.
² Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
³ Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia; Central Laboratory, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
⁴ Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, United States.
⁵ Department of Microbiology, East West Group of Institution, No. 63, Anjananagar, Vishwaneedam Post, Bangaluru 560091, Karnataka, India.
⁶ Department of Biosciences, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam, A.P. 515 134, India.

PMID: 29421701
DOI: 10.1016/j.bioorg.2018.01.019

Abstract

A small library of novel spiropyrrolidine heterocyclic hybrids has been prepared regioselectively in 1-butyl-3-methylimidazoliumbromide ([bmim]Br) with good to excellent yields using a [3+2] cycloaddition reaction. These synthesized compounds were evaluated as potential agents for treating Alzheimer's disease. Compound 4b showed the most potent activity, with an IC₅₀ of 7.9 ± 0.25 µM against acetylcholinesterase (AChE). The inhibition mechanisms for the most active compounds on AChE and butyrylcholinesterase (BChE) receptors were elucidated using molecular docking simulations.

Keywords: 1,3-dipolar cycloaddition; AChE; Alzheimer’s disease; BChE; Molecular docking study; Spiropyrrolidines.

Publication types

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

MeSH terms

Acetylcholinesterase / metabolism*
Animals
Butyrylcholinesterase / metabolism*
Cholinesterase Inhibitors / chemical synthesis
Cholinesterase Inhibitors / chemistry
Cholinesterase Inhibitors / pharmacology*
Dose-Response Relationship, Drug
Electrophorus
Horses
Ionic Liquids / chemical synthesis
Ionic Liquids / chemistry
Ionic Liquids / pharmacology*
Molecular Docking Simulation
Molecular Structure
Pyrrolidines / chemical synthesis
Pyrrolidines / chemistry
Pyrrolidines / pharmacology*
Structure-Activity Relationship

Substances

Cholinesterase Inhibitors
Ionic Liquids
Pyrrolidines
Acetylcholinesterase
Butyrylcholinesterase