Synthesis and in vitro cholinesterase inhibitory potential of dihydropyridine derivatives

Pak J Pharm Sci. 2019 May;32(3 (Supplementary)):1155-1162.

Abstract

Twelve derivatives of dihydropyridine derivatives (6-17) were synthesized and evaluated for in-vitro cholinesterases (AChE, BChE) inhibitory activity. All compounds showed potent activity with IC50 values between 0.21±0.003 to 147.14±0.12μM for AChE and among them five compounds showed potent activity with IC50 values 17.16±0.02 to 231.6±0.12μM for BChE when compared with standard Eserine (IC50 = 0.85±0.0001 μM (AChE) & 0.04±0.0001μM (BChE). The most potent compound 11 can be considered as potential lead compound showed an inhibition of 95.35±0.11 and IC50= 0.21±0.003 while compound 7 showed an inhibition of 83.45±0.13 and IC50= 17.16±0.02. It is concluded from structural activity relationship that the presence of nitro group at C-2 and C-4 position of dihydropyridine ring increase the acetyl cholinesterase and butyrylcholinesterase activities of these compounds while presence of -Br and -Cl also enhances the activities.

MeSH terms

  • Acetylcholinesterase / metabolism
  • Butyrylcholinesterase / metabolism
  • Cholinesterase Inhibitors / chemical synthesis*
  • Cholinesterase Inhibitors / pharmacology*
  • Dihydropyridines / chemical synthesis
  • Dihydropyridines / chemistry*
  • Dihydropyridines / pharmacology
  • Drug Evaluation, Preclinical
  • Magnetic Resonance Spectroscopy
  • Spectroscopy, Fourier Transform Infrared
  • Structure-Activity Relationship

Substances

  • Cholinesterase Inhibitors
  • Dihydropyridines
  • Acetylcholinesterase
  • Butyrylcholinesterase