RESUMO
Penicillin-resistant bacteria can often be treated through the co-administration of an antibiotic and a beta-lactamase inhibitor. Current inhibitors target only class A beta-lactamases. We report two new series of C3-modified penicillin sulfones, having either a simple methylene group (i.e., a homologue) or exocyclic unsaturation between the thiazolidine ring and the C3 carboxylate. The homologue has 10-fold better activity against a class C beta-lactamase than does sulbactam itself. By contrast, the exocyclic C3 unsaturated compounds are less active.
Assuntos
Técnicas de Química Combinatória , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Penicilinas/síntese química , Penicilinas/farmacologia , Inibidores de beta-Lactamases , Bactérias/enzimologia , Resistência às Penicilinas , Relação Estrutura-AtividadeRESUMO
The synthesis and beta-lactamase inhibitory activity of four 6-(mercaptomethyl)penicillinates and the four corresponding 6-(hydroxymethyl)penicillinates are described. These penicillins include both C6 stereoisomers as well as the sulfide and sulfone oxidation states of the penam thiazolidine sulfur. All compounds were evaluated as inhibitors of representative metallo- and serine-beta-lactamases enzymes. Selected (mercaptomethyl)penicillinates are shown to inactivate both metallo- and serine-beta-lactamases and to display synergism with piperacillin against beta-lactamase producing strains.
