On the search for potential anti-Trypanosoma cruzi drugs: synthesis and biological evaluation of 2-hydroxy-3-methylamino and 1,2,3-triazolic naphthoquinoidal compounds obtained by click chemistry reactions

Eur J Med Chem. 2012 Jun:52:304-12. doi: 10.1016/j.ejmech.2012.03.039. Epub 2012 Mar 29.

Abstract

Five 2-hydroxy-3-substituted-aminomethyl naphthoquinones, nine 1,2,3-triazolic para-naphthoquinones, five nor-β-lapachone-based 1,2,3-triazoles, and several other naphthoquinonoid compounds were synthesized and evaluated against the infective bloodstream form of Trypanosoma cruzi, the etiological agent of Chagas disease, continuing our screening program for new trypanocidal compounds. Among all the substances, 16-18, 23, 25-29 and 30-33 were herein described for the first time and fifteen substances were identified as more potent than the standard drug benznidazole, with IC(50)/24h values in the range of 10.9-101.5 μM. Compounds 14 and 19 with Selectivity Index of 18.9 and 6.1 are important structures for further studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemistry Techniques, Synthetic*
  • Click Chemistry*
  • Drug Discovery*
  • Mice
  • Naphthoquinones / chemical synthesis*
  • Naphthoquinones / chemistry
  • Naphthoquinones / pharmacology*
  • Naphthoquinones / toxicity
  • Triazoles / chemistry*
  • Trypanocidal Agents / chemical synthesis
  • Trypanocidal Agents / chemistry
  • Trypanocidal Agents / pharmacology
  • Trypanocidal Agents / toxicity
  • Trypanosoma cruzi / drug effects*

Substances

  • Naphthoquinones
  • Triazoles
  • Trypanocidal Agents