Synthesis and biological evaluation of solithromycin analogs against multidrug resistant pathogens

Bioorg Med Chem Lett. 2019 Jun 1;29(11):1386-1389. doi: 10.1016/j.bmcl.2019.03.038. Epub 2019 Mar 26.

Abstract

Novel antibacterial drugs that treat multidrug resistant pathogens are in high demand. We have synthesized analogs of solithromycin using Cu(I)-mediated click chemistry. Evaluation of the analogs using Minimum Inhibitory Concentration (MIC) assays against resistant Staphylococcus aureus, Escherichia coli, and multidrug resistant pathogens Enterococcus faecium and Acinetobacter baumannii showed they possess potencies similar to those of solithromycin, thus demonstrating their potential as future therapeutics to combat the existential threat of multidrug resistant pathogens.

Keywords: Antibiotic; Click chemistry; Multidrug resistance; Solithromycin.

Publication types

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

MeSH terms

  • Acinetobacter baumannii / drug effects*
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Resistance, Multiple, Bacterial / drug effects*
  • Enterococcus faecium / drug effects*
  • Escherichia coli / drug effects
  • Macrolides / chemical synthesis
  • Macrolides / chemistry
  • Macrolides / pharmacology*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Staphylococcus aureus / drug effects
  • Structure-Activity Relationship
  • Triazoles / chemical synthesis
  • Triazoles / chemistry
  • Triazoles / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Macrolides
  • Triazoles
  • solithromycin