Discovery of a novel series of semisynthetic vancomycin derivatives effective against vancomycin-resistant bacteria

J Med Chem. 2010 Mar 25;53(6):2528-33. doi: 10.1021/jm9017543.

Abstract

Novel semisynthetic vancomycin derivatives with antibacterial activity against vancomycin-resistant S. aureus (VRSA) were prepared. Replacement of Cl groups of vancomycin by Suzuki-Miyaura cross-coupling reaction, which gave the title compounds, is described for the first time. Introduction of a carbon substituent at the amino acid residue 2 of vancomycin led to an enhancement of antibacterial activity against vancomycin-resistant strains, whereas the additional introduction at the amino acid residue 6 resulted in a reduction in activity even against vancomycin-susceptible strains.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Bacteria / drug effects*
  • Bacteria / growth & development
  • Drug Discovery
  • Microbial Sensitivity Tests
  • Models, Chemical
  • Molecular Structure
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / growth & development
  • Vancomycin / chemical synthesis
  • Vancomycin / chemistry*
  • Vancomycin / pharmacology*
  • Vancomycin Resistance / drug effects*

Substances

  • Anti-Bacterial Agents
  • Vancomycin