Role of the 7 alpha-methoxy and side-chain carboxyl of moxalactam in beta-lactamase stability and antibacterial activity.
AUTOR(ES)
Murakami, K
RESUMO
The effects of the alpha-carboxyl of the phenylmalonyl side chain and the 7 alpha-methoxy group in moxalactam (6059-S) (7 beta-[2-carboxy-2-(4-hydroxyphenyl) acetamido]-7 alpha-methoxy-3[[(1-methyl-1H-tetrazol-5-y])thio] methyl]-1-oxa-1-dethia-3-cephem-4-carboxylic acid) and in the 1-sulfur congener on the stability to beta-lactamase were investigated by spectrophotometric and microbiological assays. The 7 alpha-methoxy substituent stabilized the compounds against penicillinase hydrolysis, and the alpha-carboxyl group stabilized them against cephalosporinase. An exception is the beta-lactamase produced by Proteus vulgaris, an inducible cephalosporinase, which hydrolyzed compounds having the alpha-carboxyl group but not those having the 7 alpha-methoxy group. Both substituents exerted their stabilizing effects independently, and compounds with both substituents, e.g., moxalactam (6059-S) and its 1-sulfur congener, were resistant to both penicillinases and cephalosporinases. The stabilization of the compounds to beta-lactamase hydrolysis improved their antibacterial activity against beta-lactamase-producing strains.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=181347Documentos Relacionados
- Novel plasmid-mediated beta-lactamase (MIR-1) conferring resistance to oxyimino- and alpha-methoxy beta-lactams in clinical isolates of Klebsiella pneumoniae.
- Comparative antibacterial activities of 7 alpha-methoxy cephalosporins and 7 beta-methoxyiminoacetamido cephalosporins against Bacteroides fragilis.
- Antibacterial activity and beta-lactamase stability of temocillin.
- In vitro antibacterial activity and beta-lactamase stability of a new carbapenem, BO-2727.
- In vitro antibacterial activity and beta-lactamase stability of E-0702, a new cephalosporin.
