Synthesis and antiprotozoal activity of nitazoxanide-N-methylbenzimidazole hybrids

Bioorg Med Chem Lett. 2013 Dec 15;23(24):6838-41. doi: 10.1016/j.bmcl.2013.10.011. Epub 2013 Oct 10.

Abstract

A series of a novel hybrid compounds between nitazoxanide and N-methylbenzimidazole were synthesized starting from the corresponding N-methyl-2-nitroanilines. The new hybrid compounds (1-13) were evaluated in vitro against Giardia intestinalis, Entamoeba histolytica, Trichomonas vaginalis. NTZ, MTZ and ABZ were used as drug standards. Experimental evaluations revealed all of the new compounds (1-13) were active and showed strong activity against the three protozoa, particularly with E. histolytica where the IC50 values ranged between 3 and 69 nM. Overall, compounds 2, 5, 7, 8, 9, 11 and 12 stood out with values lower than 87 nM for all three protozoa, comparatively better than the reference drugs.

Keywords: Benzimidazole; Entamoeba histolytica; Giardia intestinalis; Hybrid compounds; Nitazoxanide; Trichomonas vaginalis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiprotozoal Agents / chemical synthesis*
  • Antiprotozoal Agents / chemistry
  • Antiprotozoal Agents / pharmacology*
  • Benzimidazoles / chemical synthesis
  • Benzimidazoles / chemistry*
  • Benzimidazoles / pharmacology*
  • Drug Design
  • Entamoeba histolytica / drug effects
  • Eukaryota / drug effects*
  • Giardia lamblia / drug effects
  • Nitro Compounds
  • Thiazoles / chemistry*
  • Trichomonas vaginalis / drug effects

Substances

  • Antiprotozoal Agents
  • Benzimidazoles
  • Nitro Compounds
  • Thiazoles
  • nitazoxanide