New oxirane derivatives of 1,4-naphthoquinones and their evaluation against T. cruzi epimastigote forms

Bioorg Med Chem. 2012 Aug 15;20(16):4995-5000. doi: 10.1016/j.bmc.2012.06.027. Epub 2012 Jun 21.

Abstract

New oxirane derivatives were synthesized using six naphthoquinones as the starting materials. Our biological results showed that these oxiranes acted as trypanocidal agents against Trypanosoma cruzi with minimal cytotoxicity in the VERO cell line compared to naphthoquinones. In particular, oxirane derivative 14 showed low cytotoxicity in a mammalian cell line and exhibited better activity against epimastigote forms of T.cruzi than the current drug used to treat Chagas disease, benznidazole.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Death / drug effects
  • Cell Survival / drug effects
  • Chlorocebus aethiops
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Ethylene Oxide / analogs & derivatives
  • Ethylene Oxide / chemistry
  • Ethylene Oxide / pharmacology*
  • Models, Molecular
  • Molecular Structure
  • Naphthoquinones / chemistry*
  • Naphthoquinones / pharmacology*
  • Parasitic Sensitivity Tests
  • Structure-Activity Relationship
  • Trypanocidal Agents / chemical synthesis
  • Trypanocidal Agents / chemistry*
  • Trypanocidal Agents / pharmacology*
  • Trypanosoma cruzi / cytology
  • Trypanosoma cruzi / drug effects*
  • Trypanosoma cruzi / growth & development
  • Vero Cells

Substances

  • Naphthoquinones
  • Trypanocidal Agents
  • Ethylene Oxide
  • 1,4-naphthoquinone