Metronidazole hydrazone conjugates: Design, synthesis, antiamoebic and molecular docking studies

Bioorg Med Chem Lett. 2015 Sep 1;25(17):3545-9. doi: 10.1016/j.bmcl.2015.06.091. Epub 2015 Jul 3.

Abstract

Metronidazole hydrazone conjugates (2-13) were synthesized and screened in vitro for antiamoebic activity against HM1: IMSS strain of Entamoeba histolytica. Six compounds were found to be better inhibitors of E. histolytica than the reference drug metronidazole. These compounds showed greater than 50-60% viability against HeLa cervical cancer cell line after 72 h treatment. Also, molecular docking study was undertaken on E. histolytica thioredoxin reductase (EhTHRase) protein which showed significant binding affinity in the active site. Out of the six actives, some of the compounds showed lipophilic characteristics.

Keywords: Amoebiasis; Entamoeba histolytica; MTT-assay; Metronidazole; Thioredoxin reductase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amebicides / chemistry*
  • Amebicides / pharmacology*
  • Drug Design
  • Entamoeba histolytica / drug effects*
  • Entamoeba histolytica / enzymology
  • Entamoebiasis / drug therapy
  • Entamoebiasis / parasitology
  • HeLa Cells
  • Humans
  • Hydrazones / chemistry*
  • Hydrazones / pharmacology*
  • Metronidazole / analogs & derivatives*
  • Metronidazole / pharmacology*
  • Molecular Docking Simulation
  • Thioredoxin-Disulfide Reductase / metabolism

Substances

  • Amebicides
  • Hydrazones
  • Metronidazole
  • Thioredoxin-Disulfide Reductase