9- and 11-Substituted 4-azapaullones are potent and selective inhibitors of African trypanosoma

Eur J Med Chem. 2014 Aug 18;83:274-83. doi: 10.1016/j.ejmech.2014.06.020. Epub 2014 Jun 11.

Abstract

Trypanosomes from the "brucei" complex are pathogenic parasites endemic in sub-Saharan Africa and causative agents of severe diseases in humans and livestock. In order to identify new antitrypanosomal chemotypes against African trypanosomes, 4-azapaullones carrying α,β-unsaturated carbonyl chains in 9- or 11-position were synthesized employing a procedure with a Heck reaction as key step. Among the so prepared compounds, 5a and 5e proved to be potent antiparasitic agents with antitrypanosomal activity in the submicromolar range.

Keywords: Chalcones; Cinnamides; Human trypanosomiasis; Nagana; Paullones; Trypanosoma brucei brucei.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzazepines / chemical synthesis
  • Benzazepines / chemistry*
  • Benzazepines / pharmacology*
  • Benzazepines / toxicity
  • Cell Line
  • Cell Proliferation / drug effects
  • Drug Design*
  • Humans
  • Macrophages / drug effects
  • Mice
  • Structure-Activity Relationship
  • Trypanocidal Agents / chemical synthesis
  • Trypanocidal Agents / chemistry*
  • Trypanocidal Agents / pharmacology*
  • Trypanocidal Agents / toxicity
  • Trypanosoma brucei brucei / drug effects*
  • Trypanosoma brucei brucei / physiology
  • Trypanosomiasis, African / parasitology*

Substances

  • Benzazepines
  • Trypanocidal Agents
  • paullone