1-Oxacephalosporins: enhancement of beta-lactam reactivity and antibacterial activity.
The effect of replacement of sulfur in the cephem nucleus by oxygen upon the beta-lactamase stability, infrared carbonyl frequency of the beta-lactam ring, and antibacterial activity was investigated. The replacement reduced the stability of beta-lactam compounds to beta-lactamases, increased the IR frequencies, and enhanced the intrinsic antibacterial activity against bacterial strains without beta-lactamase. The instability of 1-oxacephalosporins to beta-lactamases, in other words, high reactivity to the enzymes, seemed to be due to the enhanced chemical reactivity of their beta-lactam rings which was indicated by their higher IR beta-lactam carbonyl frequencies. Based on a view that acylation of the enzyme by beta-lactam compounds occurred in both cases of beta-lactamase hydrolysis and target enzyme inhibition, the suggestion was made that one of the factors which conferred the higher intrinsic antibacterial activity on 1-oxacephalosporins was their high reactivity to the target enzyme(s), as was the case with beta-lactamases.
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D002510:Cephalosporinase / Q000378:metabolism; D002511:Cephalosporins / Q000138:chemical synthesis*; D002513:Cephamycins / Q000138:chemical synthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D008826:Microbial Sensitivity Tests; D009070:Moxalactam; D047090:beta-Lactams / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D002513:Cephamycins; D047090:beta-Lactams; D002510:Cephalosporinase; D009070:Moxalactam