The evaluation of quinonoid compounds against Trypanosoma cruzi: synthesis of imidazolic anthraquinones, nor-beta-lapachone derivatives and beta-lapachone-based 1,2,3-triazoles

Bioorg Med Chem. 2010 May 1;18(9):3224-30. doi: 10.1016/j.bmc.2010.03.029. Epub 2010 Mar 16.

Abstract

In continuing our screening program of naphthoquinone activity against Trypanosoma cruzi, the aetiological agent of Chagas' disease, new beta-lapachone-based 1,2,3-triazoles, 3-arylamino-nor-beta-lapachones, 3-alkoxy-nor-beta-lapachones and imidazole anthraquinones were synthesised and evaluated against bloodstream trypomastigote forms of the parasite. Compounds 2,2-dimethyl-3-(2,4-dibromophenylamino)-2,3-dihydro-naphtho[1,2-b]furan-4,5-dione, IC(50)/24h 24.9+/-7.4 and 4-azido-3-bromo-2,2-dimethyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione with 23.4+/-3.8 microM showed a trypanosomicidal activity higher than benznidazole. These results demonstrate the potential of naphthoquinone derivatives as novel structures for the development of alternative drugs for Chagas' disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anthraquinones* / chemical synthesis
  • Anthraquinones* / chemistry
  • Anthraquinones* / pharmacology
  • Antiparasitic Agents* / chemical synthesis
  • Antiparasitic Agents* / chemistry
  • Antiparasitic Agents* / pharmacology
  • Crystallography, X-Ray
  • Imidazoles / chemical synthesis
  • Imidazoles / chemistry
  • Imidazoles / pharmacology
  • Mice
  • Molecular Structure
  • Naphthoquinones* / chemical synthesis
  • Naphthoquinones* / chemistry
  • Naphthoquinones* / pharmacology
  • Parasitic Sensitivity Tests
  • Quinones / chemical synthesis
  • Quinones / chemistry
  • Quinones / pharmacology
  • Triazoles* / chemical synthesis
  • Triazoles* / chemistry
  • Triazoles* / pharmacology
  • Trypanosoma cruzi / drug effects*

Substances

  • Anthraquinones
  • Antiparasitic Agents
  • Imidazoles
  • Naphthoquinones
  • Quinones
  • Triazoles
  • beta-lapachone