Izumenolide-a novel beta-lactamase inhibitor produced by Micromonospora. II. Biological properties.
Izumenolide is a potent inhibitor of beta-lactamases, especially from Gram-negative bacteria. The I50 value of 0.01 microgram/ml for TEM-2 beta-lactamase, after 10 min preincubation, corresponds to a ratio of 7.6 moles inhibitor per mole of enzyme. The initial inhibitory reaction with TEM-2 beta-lactamase exhibits mixed reaction kinetics, suggesting a possible overlapping binding site with the active center. Tem-2 beta-lactamase is irreversible inactivated by izumenolide in a biphasic reaction. Carbenicillin offers partial protection against inactivation. Izumenolide exhibits limited antibiotic activity against some Gram-negative bacteria. Against beta-lactamase producing bacteria izumenolide provides protection to ampicillin and cephaloridine but the protection is limited due to permeability problems associated with izumenolide entry into the cells.
D000818:Animals; D001419:Bacteria / Q000187:drug effects / Q000201:enzymology; D001665:Binding Sites; D004352:Drug Resistance, Microbial; D007783:Lactones / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008847:Micromonospora / Q000378:metabolism*; D013329:Structure-Activity Relationship; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000378:metabolism
D007783:Lactones; D065093:beta-Lactamase Inhibitors; C030788:izumenolide; D001618:beta-Lactamases