Synthesis and antibacterial activity of dual-action agents of a beta-lactam antibiotic with cytotoxic agent mitozolomide or temozolomide.
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.
Wang
Yongfeng
Y
Pharmaceutical Research Institute, Aston University, Birmingham B4 7ET, UK. y.f.wang@aston.ac.uk
Lambert
Peter
P
Zhao
Linxiang
L
Wang
Danni
D
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry*; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000737:chemistry*; D024881:Drug Resistance, Bacterial; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D009588:Nitrogen Mustard Compounds / Q000737:chemistry*; D013329:Structure-Activity Relationship; D000077204:Temozolomide; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D009588:Nitrogen Mustard Compounds; D047090:beta-Lactams; D003606:Dacarbazine; C040369:mitozolomide; D000077204:Temozolomide