Synthesis of naphthofuranquinones with activity against Trypanosoma cruzi

Eur J Med Chem. 2006 Apr;41(4):526-30. doi: 10.1016/j.ejmech.2005.12.006. Epub 2006 Feb 28.

Abstract

Four new naphthofuranquinones, obtained from 2-hydroxy-3-allyl-naphthoquinone (1) and nor-lapachol (2), have their structures established by physical and X-ray analysis and their activity evaluated against Trypanosoma cruzi. Compounds 3 and 4 were obtained by addition of iodine to 1 followed by cyclization generating a furan ring. Compound 5 was obtained through the acid-catalyzed reaction by dissolution of 1 in sulfuric acid. Compound 6 was synthesized by addition of bromine and aniline to 2. The IC(50)/24 h for 3-6 in assays with T. cruzi trypomastigotes was between 157 and 640 microM, while the value for crystal violet was 536.0 +/- 3.0 microM. Compounds 3-5 also inhibited epimastigote proliferation. The trypanocidal activity of the new naphthofuranquinones endowed with redox properties reinforces a rational approach in the chemotherapy of Chagas' disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Crystallization
  • Crystallography, X-Ray
  • Indicators and Reagents
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Models, Molecular
  • Naphthoquinones / chemical synthesis*
  • Naphthoquinones / pharmacology*
  • Structure-Activity Relationship
  • Trypanocidal Agents / chemical synthesis*
  • Trypanocidal Agents / pharmacology*
  • Trypanosoma cruzi / drug effects*

Substances

  • Indicators and Reagents
  • Naphthoquinones
  • Trypanocidal Agents