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

Dual-action agents 5a-f and 12a-f, a β-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 β-lactamase producing strains. The tests showed 5a-f active against the non-β-lactamase producing methicillin sensitive Staphylococcus aureus (MSSA) strains, however, little synergistic effect between the β-lactam and the cytotoxic agent was observed. 12a-f demonstrated some synergistic effect against bacteria. 12a, in particular, is active against ampicillin resistant (β-lactamase-producing) strains of Serratia marcescens.