A synthetic gamma-lactone group with beta-lactamase inhibitory and sporulation initiation effects

J Chemother. 2000 Aug;12(4):274-9. doi: 10.1179/joc.2000.12.4.274.

Abstract

Previous studies showed that some lactones have beta-lactamase inhibitory or antibacterial effects, others--like A-factor (a gamma-butyrolactone) and its derivatives--stimulate sporulation in Streptomyces griseus strains. Our experiments were aimed at exploring whether synthetic gamma-lactones had such effects. None of the seven gamma-lactones studied showed antibacterial activity, but two of them inhibited beta-lactamases isolated from various bacteria. These two gamma-lactones did not reduce colony formation of murine bone marrow cells in vitro, indicating that they were not toxic to proliferating mammalian cells. Four gamma-lactones, including the two inhibiting beta-lactamase, stimulated sporulation in the non-sporulating S. griseus bald 7 mutant. Further studies of gamma-lactones as potential inhibitors of beta-lactamase seem to be warranted.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects*
  • Cell Division / drug effects
  • Colony-Forming Units Assay
  • Dose-Response Relationship, Drug
  • Lactones / chemical synthesis
  • Lactones / chemistry
  • Lactones / pharmacology*
  • Mice
  • Microbial Sensitivity Tests
  • Spores, Bacterial / drug effects
  • Streptomyces griseus / drug effects*
  • beta-Lactamase Inhibitors*
  • beta-Lactams / pharmacology

Substances

  • Anti-Bacterial Agents
  • Lactones
  • beta-Lactamase Inhibitors
  • beta-Lactams