Effect of 3-substitution in oxyiminocephalosporins on the stability to and the inhibition of various .BETA.-lactamases.

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Abstract
Nine 2-aminothiazolyl methoxyiminoacetamidocephems (ATOIC) and several 4-furyl methoxyiminoacetamidocephems (FOIC) were compared for stability to and inhibition of various .beta.-lactamases. Although ATOIC 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 FOIC, which, however, were in general more susceptible to those CXases than were ATOIC. The substitution of C-3 had lesser effects on the stability to some cephalosporinases (CSases) and also had little effect on the inhibitory activity of ATOIC and FOIC on various CSases, though the compound unsubstituted at C-3 (ceftizoxime) exhibited the least inhibition among ATOIC tested. The Ki 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.