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

Bioorg Med Chem. 2014 Jan 15;22(2):906-16. doi: 10.1016/j.bmc.2013.11.020. Epub 2013 Nov 19.

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.

Keywords: AChE and BChE inhibitory activity; Aromatic core multiplicity; Domino cascade synthesis; Ionic liquids; Molecular modeling; Thiazolopyrimidines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Butyrylcholinesterase / metabolism
  • Cholinesterase Inhibitors / chemical synthesis
  • Cholinesterase Inhibitors / chemistry*
  • Cholinesterase Inhibitors / pharmacology*
  • Cholinesterases / metabolism*
  • Dose-Response Relationship, Drug
  • Green Chemistry Technology*
  • Humans
  • Molecular Docking Simulation*
  • Molecular Structure
  • Piperidones / chemistry*
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Cholinesterase Inhibitors
  • Piperidones
  • Pyrimidines
  • Butyrylcholinesterase
  • Cholinesterases