Effect of 3-Substitution in Oxyiminocephalosporins on the Stability to and the Inhibition of Various β-Lactamases

概要

論文の詳細を見る
Nine 2-aminothiazolyl methoxyiminoacetamidocephems (ATOICs) as well as several 4-furyl methoxyiminoacetamidocephems (FOICs) were compared for stability to and inhibition of various β-lactamases. Although ATOICs are generally less stable to cefuroxymases (CXases) from Proteus vulgaris or Bacteroides fragilis, the relative susceptibility among them was greatly affected by the substitution at the 3-position : the compound unsubstituted at C-3 was most stable, while thiomethyleno-2-methyl-6-hydroxytriazine-5-one substitution gave the most labile compound. A similar tendency was also seen with FOICs, which, however, were in general more susceptible to those CXases than were ATOICs. The substitution at C-3 had lesser effects on the stability to some cephalosporinases (CSases), and also had little effect on the inhibitory activity of ATOICs and FOICs on various CSases, though the compound unsubstituted at C-3 (ceftizoxime) exhibited the least inhibition among ATOICs tested. The K_i values of typical ATOICs except ceftizoxime were 10^<-8>-10^<-9>M for enzymes from Citrobacter freundii, and Enterobacter sp. and 10^<-6>-10^<-7>M for those from Escherichia coli, Serratia marcescens and Pseudomonas aeruginosa.
公益社団法人日本薬学会の論文
1982-09-25