Synthesis and in vitro evaluation of potential antichagasic hydroxymethylnitrofurazone (NFOH-121): a new nitrofurazone prodrug

Bioorg Med Chem. 2003 Nov 3;11(22):4779-83. doi: 10.1016/j.bmc.2003.07.004.

Abstract

The synthesis of mutual prodrugs of nitrofurazone with primaquine, using specific and nonspecific spacer groups, has been previously attempted seeking selective antichagasic agents. The intermediate reaction product, hydroxymethylnitrofurazone (NFOH-121), was isolated and tested in LLC-MK(2) culture cells infected with trypomastigotes forms of Trypanosoma cruzi showing higher trypanocidal activity than nitrofurazone and benznidazol in all stages. The mutagenicity tests showed that the prodrug was less toxic than the parent drug. Degradation assays were carried out in pH 1.2 and 7.4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Chagas Disease
  • Macaca mulatta
  • Mutagenicity Tests / methods
  • Nitrofurazone / analogs & derivatives*
  • Nitrofurazone / chemical synthesis*
  • Nitrofurazone / metabolism
  • Nitrofurazone / pharmacology*
  • Prodrugs / chemical synthesis*
  • Prodrugs / chemistry
  • Prodrugs / metabolism
  • Prodrugs / pharmacology*
  • Spectrophotometry, Ultraviolet
  • Trypanocidal Agents / chemical synthesis*
  • Trypanocidal Agents / metabolism
  • Trypanocidal Agents / pharmacology*
  • Trypanosoma cruzi / drug effects
  • Trypanosoma cruzi / physiology

Substances

  • Prodrugs
  • Trypanocidal Agents
  • hydroxymethylnitrofurazone
  • Nitrofurazone