Synthesis and biological evaluation of α-hydroxyalkylphosphonates as new antimicrobial agents

Bioorg Med Chem Lett. 2014 Jan 1;24(1):49-53. doi: 10.1016/j.bmcl.2013.12.002. Epub 2013 Dec 8.

Abstract

A set of α-quaternary 3-chloro-1-hydroxyalkylphosphonates, analogues of fosfomycin and fosfonochlorin, some of which are new compounds, was synthesized. The compounds were screened for bioactivity against several clinical and standard microbial isolates. Some were found to have moderate activity. The activity was higher with phenyl protection of the phosphoryl ester groups and α-phenyl substitution. Compound 11 was as effective or more potent than fosfomycin or chloramphenicol against several Gram-negative bacteria as well as against some Gram-positive ones.

Keywords: Antimicrobial activity; Clinical isolates; Gram-negative; Gram-positive; Phosphonates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Gram-Negative Bacteria / drug effects*
  • Gram-Positive Bacteria / drug effects*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Organophosphonates / chemical synthesis
  • Organophosphonates / chemistry
  • Organophosphonates / pharmacology*
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Organophosphonates