Synthesis and antikinetoplastid activities of 3-substituted quinolinones derivatives

Eur J Med Chem. 2012 Jun:52:44-50. doi: 10.1016/j.ejmech.2012.03.003. Epub 2012 Mar 16.

Abstract

A new family of quinolinone derivatives has been synthesized and evaluated for their antikinetoplastid activities against Leishmania donovani and Trypanosoma brucei brucei. Results from these structure-activity relationship studies enabled identification of compounds 3a and 4g as the most active compounds against L. donovani promastigotes and amastigotes parasites (IC(50) values in a range of 2-11 μM). Additionally, compound 3b has emerged from this study as the most active compound in the series against T. b. brucei with a MEC value of 12 μM. These three compounds are worth of further in vivo evaluation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiprotozoal Agents / chemical synthesis*
  • Antiprotozoal Agents / chemistry
  • Antiprotozoal Agents / pharmacology*
  • Antiprotozoal Agents / toxicity
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Design
  • Leishmania donovani / drug effects*
  • Mice
  • Quinolones / chemical synthesis*
  • Quinolones / chemistry
  • Quinolones / pharmacology*
  • Quinolones / toxicity
  • Structure-Activity Relationship
  • Trypanosoma brucei brucei / drug effects*

Substances

  • Antiprotozoal Agents
  • Quinolones