title: beta-Lactamase hydrolysis of cephalosporin 3'-quinolone esters, carbamates, and tertiary amines.
abstract: The beta-lactam hydrolysis of five cephalosporin 3'-quinolones (dual-action cephalosporins) by three gram-negative beta-lactamases was examined. The dual-action cephalosporins tested were the ester Ro 23-9424; the carbamates Ro 25-2016, Ro 25-4095, and Ro 25-4835; and the tertiary amine Ro 25-0534. Also tested were cephalosporins with similar side chains (cefotaxime, desacetylcefotaxime, cephalothin, cephacetrile, and Ro 09-1227 [SR 0124]) and standard beta-lactams (penicillin G, cephaloridine). The beta-lactamases used were the plasmid-mediated TEM-1 and TEM-3 enzymes and the chromosomal AmpC. The cephacetrile-related compounds Ro 25-4095 and Ro 25-4835 were hydrolyzed by all three beta-lactamases with catalytic efficiencies (relative to penicillin G) ranging from approximately 5 (TEM-1, AmpC) to approximately 25 (TEM-3). The cephalothin-related Ro 25-2016 was also hydrolyzed by all three beta-lactamases, particularly the AmpC enzyme (relative catalytic efficiency, 110). The cefotaxime-related compounds Ro 25-0534 and Ro 23-9424 were hydrolyzed to any significant extent only by the TEM-3 enzyme (relative catalytic efficiencies, 1.2 and 4.7, respectively.
authors.affiliation: Department of Antibacterial Research, Roche Research Center, Nutley, NJ 07110-1199.
authors.forename: N H
authors.initials: NH
authors.lastname: Georgopapadakou
authors.forename: C
authors.initials: C
authors.lastname: McCaffrey
mesh_terms: D000588:Amines / Q000378:metabolism*; D000890:Anti-Infective Agents / Q000378:metabolism*; D002219:Carbamates / Q000378:metabolism*; D002439:Cefotaxime / Q000031:analogs & derivatives* / Q000378:metabolism; D004952:Esters / Q000378:metabolism; D016576:Fleroxacin / Q000031:analogs & derivatives* / Q000378:metabolism; D024841:Fluoroquinolones; D006868:Hydrolysis; D007700:Kinetics; D010957:Plasmids; D001618:beta-Lactamases / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D000588:Amines; D000890:Anti-Infective Agents; D002219:Carbamates; D004952:Esters; D024841:Fluoroquinolones; C060441:Ro-23-9424; D001618:beta-Lactamases; C034413:beta-lactamase TEM-1; C056342:beta-lactamase TEM-2; D002439:Cefotaxime; D016576:Fleroxacin