Biology-oriented drug synthesis (BIODS) of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl aryl ether derivatives, in vitro α-amylase inhibitory activity and in silico studies

Bioorg Chem. 2017 Oct:74:1-9. doi: 10.1016/j.bioorg.2017.07.001. Epub 2017 Jul 11.

Abstract

A new library of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl aryl ether derivatives (1-23) were synthesized and characterized by EI-MS and 1H NMR, and screened for their α-amylase inhibitory activity. Out of twenty-three derivatives, two molecules 19 (IC50=0.38±0.82µM) and 23 (IC50=1.66±0.14µM), showed excellent activity whereas the remaining compounds, except 10 and 17, showed good to moderate inhibition in the range of IC50=1.77-2.98µM when compared with the standard acarbose (IC50=1.66±0.1µM). A plausible structure-activity relationship has also been presented. In addition, in silico studies was carried out in order to rationalize the binding interaction of compounds with the active site of enzyme.

Keywords: BIODS; In silico; In vitro; Metronidazole; Structure-activity relationship (SAR); Synthesis; α-amylase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Ether / chemical synthesis
  • Ether / chemistry
  • Ether / pharmacology*
  • Imidazoles / chemical synthesis
  • Imidazoles / chemistry
  • Imidazoles / pharmacology*
  • Molecular Docking Simulation*
  • Molecular Structure
  • Structure-Activity Relationship
  • Swine
  • alpha-Amylases / antagonists & inhibitors*
  • alpha-Amylases / metabolism

Substances

  • Enzyme Inhibitors
  • Imidazoles
  • Ether
  • alpha-Amylases