Teaching 'old' polymyxins new tricks: new-generation lipopeptides targeting gram-negative 'superbugs'

ACS Chem Biol. 2014 May 16;9(5):1172-7. doi: 10.1021/cb500080r. Epub 2014 Mar 17.

Abstract

The antimicrobial lipopeptides polymyxin B and E (colistin) are being used as a 'last-line' therapy for infections caused by multidrug-resistant Gram-negative pathogens. Polymyxin resistance implies a total lack of antibiotics for the treatment of life-threatening infections caused by the Gram-negative 'superbugs'. This report details the structure-activity relationships (SAR) based design, in toto synthesis, and preclinical evaluation of a series of novel polymyxin lipopeptides with better antibacterial activity against polymyxin-resistant Gram-negative bacteria.

Publication types

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

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Drug Resistance, Multiple, Bacterial
  • Gram-Negative Bacteria / drug effects*
  • Gram-Negative Bacterial Infections / drug therapy
  • Humans
  • Mice
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Polymyxins / chemistry*
  • Polymyxins / pharmacology*
  • Polymyxins / therapeutic use
  • Pseudomonas Infections / drug therapy
  • Pseudomonas aeruginosa / drug effects
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Polymyxins