Synthesis and anti-Trypanosoma cruzi activity of β-lapachone analogues

Eur J Med Chem. 2011 Jul;46(7):3071-7. doi: 10.1016/j.ejmech.2011.03.012. Epub 2011 Mar 15.

Abstract

The available chemotherapy for Chagas disease, caused by Trypanosoma cruzi, is unsatisfactory; therefore, there is an intense effort to find new drugs for the treatment of this disease. In our laboratory, we have analyzed the effect on bloodstream trypomastigotes of 16 new naphthoquinone analogues of β-lapachone modified in the pyran ring, aiming to find a new prototype with high trypanocidal activity. The new compounds presented a broad spectrum of activity, and five of them presented IC(50)/24 h in the range of 22-63 μM, whereas β-lapachone had a higher value of 391.5 ± 16.5 μM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Cells / drug effects
  • Blood Cells / parasitology
  • Chagas Disease / parasitology
  • Inhibitory Concentration 50
  • Life Cycle Stages / drug effects*
  • Life Cycle Stages / physiology
  • Mice
  • Naphthoquinones / chemical synthesis*
  • Naphthoquinones / pharmacology
  • Pyrans / chemistry
  • Structure-Activity Relationship
  • Trypanocidal Agents / chemical synthesis*
  • Trypanocidal Agents / pharmacology
  • Trypanosoma cruzi / drug effects*
  • Trypanosoma cruzi / growth & development

Substances

  • Naphthoquinones
  • Pyrans
  • Trypanocidal Agents
  • beta-lapachone