Synthesis, structure-activity relationship and in vitro anti-mycobacterial evaluation of 13-n-octylberberine derivatives

Eur J Med Chem. 2012 Jun:52:151-8. doi: 10.1016/j.ejmech.2012.03.012. Epub 2012 Mar 21.

Abstract

Twenty-eight new 13-n-octylberberine derivatives were synthesized and evaluated for their activities against drug-susceptible Mycobacterium tuberculosis (M. tuberculosis) strain H(37)Rv. Among these compounds, compound 16e was the most effective anti-tubercular agent with a MIC value of 0.125 μg/mL. Importantly, compound 16e exhibited more potent effect against rifampicin (RIF)- and isoniazid (INH)-resistant M. tuberculosis strains than both RIF and INH, suggesting a new mechanism of action. Therefore, it has been selected as a drug candidate for further investigation, or as a chemical probe for identifying protein target and studying tuberculosis biology. We consider 13-n-octylberberine analogs to be a promising novel class of antituberculars against multi-drug-resistant (MDR) strains of M. tuberculosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Berberine / analogs & derivatives*
  • Berberine / chemical synthesis*
  • Berberine / chemistry
  • Berberine / pharmacology*
  • Chemistry Techniques, Synthetic*
  • Drug Resistance, Bacterial / drug effects
  • Mycobacterium tuberculosis / drug effects*
  • Structure-Activity Relationship

Substances

  • 13-n-octylberberine
  • Anti-Bacterial Agents
  • Berberine