Bottromycin derivatives: efficient chemical modifications of the ester moiety and evaluation of anti-MRSA and anti-VRE activities

Bioorg Med Chem Lett. 2010 Oct 15;20(20):6116-20. doi: 10.1016/j.bmcl.2010.08.037. Epub 2010 Aug 18.

Abstract

Novel bottromycin derivatives were synthesized from bottromycin A(2) via a hydrazide derivative as a common intermediate. Seventeen derivatives were subjected to in vitro evaluation against drug-resistant gram-positive bacteria. Some compounds showed potent anti-MRSA and anti-VRE activity, as did bottromycin A(2). Notably, a propyl ketone derivative exhibited good antibacterial activity with excellent metabolite stability.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology*
  • Drug Resistance, Bacterial
  • Enterococcaceae / drug effects
  • Gram-Positive Bacteria / drug effects*
  • Gram-Positive Bacterial Infections / drug therapy
  • Humans
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Mice
  • Microbial Sensitivity Tests
  • Peptides, Cyclic / chemical synthesis
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / metabolism
  • Peptides, Cyclic / pharmacology
  • Plasma / metabolism
  • Vancomycin / pharmacology

Substances

  • Anti-Bacterial Agents
  • Peptides, Cyclic
  • bottromycin A(2)
  • Vancomycin