Penicillin-derived inhibitors that simultaneously target both metallo- and serine-beta-lactamases.
The synthesis and beta-lactamase inhibitory activity of four 6-(mercaptomethyl)penicillinates and the four corresponding 6-(hydroxymethyl)penicillinates are described. These penicillins include both C6 stereoisomers as well as the sulfide and sulfone oxidation states of the penam thiazolidine sulfur. All compounds were evaluated as inhibitors of representative metallo- and serine-beta-lactamases enzymes. Selected (mercaptomethyl)penicillinates are shown to inactivate both metallo- and serine-beta-lactamases and to display synergism with piperacillin against beta-lactamase producing strains.
Buynak
John D
JD
Department of Chemistry, Southern Methodist University, Dallas, TX 75275-0314, USA. jbuynak@mail.smu.edu
Chen
Hansong
H
Vogeti
Lakshminaryana
L
Gadhachanda
Venkat Rao
VR
Buchanan
Christine A
CA
Palzkill
Timothy
T
Shaw
Robert W
RW
Spencer
James
J
Walsh
Timothy R
TR
D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D010406:Penicillins / Q000737:chemistry* / Q000494:pharmacology; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D012269:Ribosomal Proteins / Q000037:antagonists & inhibitors*; D012694:Serine; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000378:metabolism
D008565:Membrane Proteins; D010406:Penicillins; D011480:Protease Inhibitors; D012269:Ribosomal Proteins; D065093:beta-Lactamase Inhibitors; D012694:Serine; D001618:beta-Lactamases