The inhibition of metallo-beta-lactamase by thioxo-cephalosporin derivatives.
The 8-thioxocephalosporins are poor substrates for the B. cereus metallo beta-lactamase (k(cat)/K(m)=61.4M(-1) s(-1)) and act as weak competitive inhibitors (K(i) approximately 700 microM). The hydrolysis product of thioxocephalosporin, a thioacid, also inhibits the enzyme competitively with a K(i)=96 microM, whereas the cyclic thioxo-piperazinedione, formed by intramolecular aminolysis of thioxocephalexin has a K(i) of 29 microM.
Tsang
Wing Y
WY
Department of Chemical and Biological Sciences, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, UK.
Dhanda
Anupma
A
Schofield
Christopher J
CJ
Frère
Jean-Marie
JM
Galleni
Moreno
M
Page
Michael I
MI
D001409:Bacillus cereus / Q000187:drug effects / Q000201:enzymology; D002511:Cephalosporins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000378:metabolism
D002511:Cephalosporins; D004791:Enzyme Inhibitors; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases