Synthesis of benzologues of Nitazoxanide and Tizoxanide: a comparative study of their in vitro broad-spectrum antiprotozoal activity

Bioorg Med Chem Lett. 2011 May 15;21(10):3168-71. doi: 10.1016/j.bmcl.2011.02.100. Epub 2011 Feb 26.

Abstract

We have synthesized two new benzologues of Nitazoxanide (NIT) and Tizoxanide (TIZ), using a short synthetic route. Both compounds were tested in vitro against six protozoa (Giardia intestinalis, Trichomonas vaginalis, Entamoeba histolytica, Plasmodium berghei, Leishmania mexicana and Trypanosoma cruzi). Compound 1 (benzologue of NIT) showed broad antiprotozoal effect against all parasites tested, showing IC(50)'s<5 μM. This compound was five-times more active than NIT, and 18-times more potent than metronidazole against G. intestinalis. It was 10-times more active than pentamidine against L. mexicana, and it was sevenfold more potent than benznidazole versus T. cruzi. This compound could be considered as a new broad spectrum antiprotozoal agent.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiprotozoal Agents / chemical synthesis*
  • Antiprotozoal Agents / pharmacology*
  • Giardia / drug effects
  • Molecular Structure
  • Nitro Compounds
  • Plasmodium / drug effects
  • Thiazoles* / chemical synthesis
  • Thiazoles* / pharmacology
  • Trichomonas vaginalis / drug effects

Substances

  • Antiprotozoal Agents
  • Nitro Compounds
  • Thiazoles
  • tizoxanide
  • nitazoxanide