An evolved oxazolidinone with selective potency against Mycobacterium tuberculosis and gram positive bacteria

Bioorg Med Chem Lett. 2016 Aug 1;26(15):3572-6. doi: 10.1016/j.bmcl.2016.06.019. Epub 2016 Jun 9.

Abstract

Innovation of new antibacterials that are effective against strains that have developed resistance to existing drugs would strengthen our ability to treat and subsequently control spread of pathogenic bacteria. Increasing incidence of infections with drug resistant bacteria has become a common occurrence in recent times. We have developed an evolved oxazolidinone, T145, which inhibits growth of Enterococcus faecalis, Staphylococcus aureus and Mycobacterium tuberculosis (Mtb) with sub μg/ml potencies that are potentially therapeutically valuable. The oxazolidinone is bactericidal against Mtb but bacteriostatic against E. faecalis and S. aureus. In addition to therapeutically valuable potency and bactericidal activity against Mtb, T145 minimizes selection of spontaneous resistant mutants, a trait that prolongs longevity of a drug in clinical use.

Keywords: Antimicrobials; E. faecalis; Mycobacterium tuberculosis; Oxazolidinone; Staphylococcus aureus.

Publication types

  • Research Support, N.I.H., Extramural
  • 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-Negative Bacteria / growth & development
  • Gram-Positive Bacteria / drug effects*
  • Gram-Positive Bacteria / growth & development
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Oxazolidinones / chemical synthesis
  • Oxazolidinones / chemistry
  • Oxazolidinones / pharmacology*
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Oxazolidinones