Synthesis, antiamoebic activity and docking studies of metronidazole-triazole-styryl hybrids

Eur J Med Chem. 2018 Apr 25:150:633-641. doi: 10.1016/j.ejmech.2018.03.033. Epub 2018 Mar 13.

Abstract

A series of 22 novel metronidazole-triazole-styryl hybrids were synthesized and evaluated for their in vitro antiamoebic activity against HM1: IMSS strain of Entamoeba histolytica. Some of the hybrids were found to be more active (IC50 = 0.12-0.35 μM) than the reference drug metronidazole (IC50 = 1.79 μM). The most active compounds were found to be non-toxic (up to 50 μM) against the Vero cells showing a good safety profile of these hybrids. The docking and ADMET studies were also conducted to investigate the probable mode of action. Docking studies showed significant binding affinity in the active site of E. histolytica thioredoxin reductase (EhTrR) protein.

Keywords: Docking studies; Entamoeba histolytica; Metronidazole; Thioredoxin reductase; Triazole.

MeSH terms

  • Antiprotozoal Agents / chemical synthesis
  • Antiprotozoal Agents / chemistry
  • Antiprotozoal Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Entamoeba histolytica / drug effects*
  • Entamoeba histolytica / enzymology
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Metronidazole / chemistry
  • Metronidazole / pharmacology*
  • Molecular Docking Simulation
  • Molecular Structure
  • Parasitic Sensitivity Tests
  • Structure-Activity Relationship
  • Styrene / chemistry
  • Styrene / pharmacology*
  • Thioredoxin-Disulfide Reductase / antagonists & inhibitors
  • Thioredoxin-Disulfide Reductase / metabolism
  • Triazoles / chemistry
  • Triazoles / pharmacology*

Substances

  • Antiprotozoal Agents
  • Enzyme Inhibitors
  • Triazoles
  • Metronidazole
  • Styrene
  • Thioredoxin-Disulfide Reductase