Optimizing the antibacterial activity of a lead structure discovered by "SAR by MS" technology

Bioorg Med Chem Lett. 2004 Nov 1;14(21):5257-61. doi: 10.1016/j.bmcl.2004.08.033.

Abstract

We report on lead optimization of a compound that was originally discovered to bind bacterial 23S rRNA near the L11 binding site and inhibit translation in vitro, but lacked detectable antibacterial activity. In this study, we were able to generate compounds with antibacterial activity against Gram-negative and Gram-positive pathogens, including a methicillin-resistant S. aureus strain.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Furans / chemical synthesis*
  • Furans / chemistry
  • Furans / pharmacology
  • Gram-Negative Bacteria / drug effects
  • Gram-Positive Bacteria / drug effects
  • Mass Spectrometry
  • Methicillin Resistance
  • Microbial Sensitivity Tests
  • Piperazines / chemical synthesis*
  • Piperazines / chemistry
  • Piperazines / pharmacology
  • RNA, Ribosomal, 23S / metabolism
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Furans
  • Piperazines
  • RNA, Ribosomal, 23S