Interaction of Ro 17-2301 (AMA-1080) with beta-lactamases.
Against a variety of beta-lactamases tested, mostly of chromosomal origin, Ro 17-2301 (AMA-1080) proved to be more stable than the new cephalosporins and thus resembles aztreonam. Against the beta-lactamases from Klebsiella oxytoca and Pseudomonas vulgaris, however, Ro 17-2301 proved to be much more stable than aztreonam. Enzymatic hydrolysis, performed with the K. oxytoca beta-lactamase, yielded a single compound, viz. the microbiologically inactive, ring-opened structure. Ro 17-2301 is a potent and progressive inhibitor of cephalosporinases found, e.g., in Enterobacter cloacae and other gram-negative organisms. The IC50 and Ki values, however, showed that the affinity for these enzymes is lower than that of aztreonam.
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001398:Aztreonam / Q000031:analogs & derivatives; D004355:Drug Stability; D006868:Hydrolysis; D007700:Kinetics; D013056:Spectrophotometry, Ultraviolet / Q000379:methods; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D065093:beta-Lactamase Inhibitors; C044145:carumonam; D001618:beta-Lactamases; D001398:Aztreonam