Cholinesterase inhibitory activity versus aromatic core multiplicity: a facile green synthesis and molecular docking study of novel piperidone embedded thiazolopyrimidines

Basiri A 1 , Murugaiyah V 2 , Osman H 3 , Kumar RS 4 , Kia Y 3 , Hooda A 5 Show all authors , Parsons RB 5

Affiliations 

  • 1 School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia
  • 2 School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia. Electronic address: vicky@usm.my
  • 3 School of Chemical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia
  • 4 Department of Chemistry, College of Sciences, King Saud University, PO Box 2455, Riyadh, Saudi Arabia. Electronic address: sraju@ksu.edu.sa
  • 5 Institute of Pharmaceutical Science, King's College London, London SE1 9NH, UK
Bioorg Med Chem, 2014 Jan 15;22(2):906-16.
PMID: 24369842 DOI: 10.1016/j.bmc.2013.11.020

Abstract

Novel thiazolopyrimidine derivatives have been synthesized via microwave assisted, domino cascade methodology in ionic liquid and evaluated in vitro for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities. Among the newly synthesized compounds 6d, 6a, 6e and 6b displayed higher AChE inhibitory activity than standard drug, galanthamine, with IC50 values of 0.53, 1.47, 1.62 and 2.05μM, respectively. Interestingly, all the compounds except for 6m-r and 6x displayed higher BChE inhibitory potentials than galanthamine with IC50 values ranging from 1.09 to 18.56μM. Molecular docking simulations for 6d possessing the most potent AChE and BChE inhibitory activities, disclosed its binding interactions at the active site gorge of AChE and BChE enzymes.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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