A Synthetic γ-Lactone Group with β-Lactamase Inhibitory and Sporulation Initiation Effects

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.

A Review of the Pharmacological Activities and Recent Synthetic Advances of γ-Butyrolactones

“…Many γ-butyrolactone-containing small molecules have been studied in the development of antibiotics. Lactivicin (Entry 17) [42,43], produced by two strains of bacteria, and one bicyclic butyrolacone (Entry 18) [44] showed strong inhibition of β-lactamase with IC 50 values of 2.4 µg/mL and 15 µg/mL, respectively. Moreover, various synthetic γ-butyrolactones exhibited potent antibacterial activities.…”