Synthesis and evaluation of 3-(carboxymethylidene)- and 3-(carboxymethyl)penicillinates as inhibitors of beta-lactamase.
Penicillin-resistant bacteria can often be treated through the co-administration of an antibiotic and a beta-lactamase inhibitor. Current inhibitors target only class A beta-lactamases. We report two new series of C3-modified penicillin sulfones, having either a simple methylene group (i.e., a homologue) or exocyclic unsaturation between the thiazolidine ring and the C3 carboxylate. The homologue has 10-fold better activity against a class C beta-lactamase than does sulbactam itself. By contrast, the exocyclic C3 unsaturated compounds are less active.
Buynak
John D
JD
Department of Chemistry, Southern Methodist University, Dallas, TX 75275-0314, USA. jbuynak@smu.edu
Ghadachanda
Venkat Rao
VR
Vogeti
Lakshminaryana
L
Zhang
Hongming
H
Chen
Hansong
H
D001419:Bacteria / Q000201:enzymology; D020650:Combinatorial Chemistry Techniques; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D010403:Penicillin Resistance; D010406:Penicillins / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D065093:beta-Lactamase Inhibitors
D004791:Enzyme Inhibitors; D010406:Penicillins; D065093:beta-Lactamase Inhibitors