New bisanthraquinone antibiotics and semi-synthetic derivatives with potent activity against clinical Staphylococcus aureus and Enterococcus faecium isolates

Bioorg Med Chem. 2006 Dec 15;14(24):8446-54. doi: 10.1016/j.bmc.2006.08.038. Epub 2006 Sep 18.

Abstract

The escalation of antibiotic resistance among Gram-positive pathogens presents increasing treatment challenges and requires the development of innovative therapeutic agents. Here, we present the antimicrobial properties of structurally unusual bisanthraquinone metabolites produced by a marine streptomycete and four semi-synthetic derivatives. Biological activities were measured against clinically derived isolates of vancomycin-resistant Enterococcus faecium (VRE), and methicillin-susceptible, methicillin-resistant, and tetracycline-resistant Staphylococcus aureus (MSSA, MRSA, and TRSA, respectively). The most potent antibiotic displayed MIC(50) values of 0.11, 0.23, and 0.90microM against a panel (n=25 each) of clinical MSSA, MRSA, and VRE, respectively, and was determined to be bactericidal by time-kill analysis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anthraquinones / chemistry
  • Anthraquinones / isolation & purification
  • Anthraquinones / pharmacology*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / isolation & purification
  • Anti-Bacterial Agents / pharmacology*
  • Cells, Cultured / drug effects
  • Enterococcus faecium / drug effects*
  • Gram-Positive Bacterial Infections / drug therapy*
  • Gram-Positive Bacterial Infections / microbiology
  • Humans
  • Methicillin Resistance
  • Microbial Sensitivity Tests
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / microbiology
  • Staphylococcus aureus / drug effects*
  • Tetracycline Resistance
  • Vancomycin Resistance
  • Virginiamycin

Substances

  • Anthraquinones
  • Anti-Bacterial Agents
  • Virginiamycin