Synthesis and biological characterization of new aryloxyindole-4,9-diones as potent trypanosomicidal agents

Bioorg Med Chem Lett. 2014 Aug 15;24(16):3919-22. doi: 10.1016/j.bmcl.2014.06.044. Epub 2014 Jun 24.

Abstract

A new indole-4,9-dione and their phenoxy derivatives were synthesized and evaluated in vitro against the epimastigote form of Trypanosoma cruzi, Y strain. All of these novel compounds were found to be extremely potent and selective that the standard drug nifurtimox. Interestingly, phenoxyindole-4,9-dione 9d displayed excellent nanomolar inhibitory activity, IC50=20 nM, and high selectivity index, SI=625. In silico studies using MOE program were performed to generate a preliminary pharmacophore model.

Keywords: Anti-T. cruzi; Cytotoxicity; Indolequinones; Pharmacophore model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dose-Response Relationship, Drug
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Molecular Structure
  • Parasitic Sensitivity Tests
  • Structure-Activity Relationship
  • Trypanocidal Agents / chemical synthesis*
  • Trypanocidal Agents / chemistry
  • Trypanocidal Agents / pharmacology*
  • Trypanosoma cruzi / drug effects*

Substances

  • Indoles
  • Trypanocidal Agents