New Ianthelliformisamine derivatives as antibiotic enhancers against resistant Gram-negative bacteria

J Med Chem. 2014 May 22;57(10):4263-72. doi: 10.1021/jm500194e. Epub 2014 May 13.

Abstract

A series consisting of ianthelliformisamimes A, B, and C as well as its synthetic analogues was prepared in high chemical yield, from 27 to 91%, using peptide coupling as the key step, and the compounds were evaluated for their in vitro antibiotic enhancer properties against resistant Gram-negative bacteria and clinical isolates. The mechanism of action of one of these derivatives against Pseudomonas aeruginosa when combined with doxycycline was precisely evaluated utilizing bioluminescence to measure ATP efflux and fluorescence to evaluate membrane depolarization.

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / pharmacology
  • Gram-Negative Bacteria / drug effects*
  • Humans
  • Microbial Sensitivity Tests
  • Pseudomonas aeruginosa / drug effects
  • Tyrosine / analogs & derivatives
  • Tyrosine / pharmacology

Substances

  • Anti-Bacterial Agents
  • ianthelliformisamine A
  • ianthelliformisamine B
  • ianthelliformisamine C
  • Tyrosine