Synthesis and antibacterial activity of dual-action agents of a beta-lactam antibiotic with cytotoxic agent mitozolomide or temozolomide.

摘要

Dual-action agents 5a-f and 12a-f, a beta-lactam antibiotic combined with a cytotoxic agent, mitozolomide (Meto) or temozolomide (Temo), were synthesised. The antibacterial activity (MICs) of the dual-action agents has been determined against a panel of bacteria including several beta-lactamase producing strains. The tests showed 5a-f active against the non-beta-lactamase producing methicillin sensitive Staphylococcus aureus (MSSA) strains, however, little synergistic effect between the beta-lactam and the cytotoxic agent was observed. 12a-f demonstrated some synergistic effect against bacteria. 12a, in particular, is active against ampicillin resistant (beta-lactamase-producing) strains of Serratia marcescens.