Design, synthesis, and evaluation of efflux substrate-metal chelator conjugates as potential antimicrobial agents

Bioorg Med Chem Lett. 2007 Feb 1;17(3):707-11. doi: 10.1016/j.bmcl.2006.10.094. Epub 2006 Nov 2.

Abstract

Maintaining a proper balance of metal concentrations is critical to the survival of bacteria. We have designed and synthesized a series of conjugates of metal chelators and efflux transporter substrates aimed at disrupting bacterial metal homeostasis to achieve bacterial killing. Biological studies showed that two of the compounds had very significant antimicrobial effect with an MIC value of 7.8 microg/mL against Gram-positive Bacillus subtilis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / pharmacology*
  • Bacillus subtilis / drug effects
  • Bacteria / drug effects
  • Bacteria / metabolism
  • Chelating Agents / chemical synthesis*
  • Chelating Agents / pharmacology*
  • Drug Design
  • Drug Resistance, Multiple, Bacterial
  • Escherichia coli / drug effects
  • Indicators and Reagents
  • Metals / metabolism
  • Microbial Sensitivity Tests
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Chelating Agents
  • Indicators and Reagents
  • Metals