Synthesis of octapeptin C4 and biological profiling against NDM-1 and polymyxin-resistant bacteria

Bioorg Med Chem Lett. 2017 Jun 1;27(11):2407-2409. doi: 10.1016/j.bmcl.2017.04.027. Epub 2017 Apr 12.

Abstract

The first synthesis of octapeptin C4 was achieved using a combination of solid phase synthesis and off-resin cyclisation. Octapeptin C4 displayed antibiotic activity against multi-drug resistant, NDM-1 and polymyxin-resistant Gram-negative bacteria, with moderate activity against Staphylococcus aureus. The linear analogue of octapeptin C4 was also prepared, which showed reduced activity.

Keywords: Antibiotic; Colistin; Drug resistance; Lipopeptide; Natural product.

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / toxicity
  • Cyclization
  • Drug Resistance, Bacterial
  • Gram-Negative Bacteria / drug effects
  • Lipopeptides / chemical synthesis
  • Lipopeptides / pharmacology*
  • Lipopeptides / toxicity
  • Peptides, Cyclic / chemical synthesis
  • Peptides, Cyclic / pharmacology*
  • Peptides, Cyclic / toxicity
  • Polymyxin B / pharmacology
  • Solid-Phase Synthesis Techniques
  • Staphylococcus aureus / drug effects

Substances

  • Anti-Bacterial Agents
  • Lipopeptides
  • Peptides, Cyclic
  • octapeptin C4
  • Polymyxin B