The inhibition of metallo-β-lactamase by thioxo-cephalosporin derivatives

Wing Y. Tsang; Anupma Dhanda; Christopher J. Schofield; Jean Marie Frère; Moreno Galleni; Michael I. Page

doi:10.1016/j.bmcl.2004.01.047

The inhibition of metallo-β-lactamase by thioxo-cephalosporin derivatives

Wing Y. Tsang, Anupma Dhanda, Christopher J. Schofield, Jean Marie Frère, Moreno Galleni, Michael I. Page

School of Applied Sciences

Research output: Contribution to journal › Article › peer-review

27 Citations (Scopus)

Abstract

The 8-thioxocephalosporins are poor substrates for the B. cereus metallo β-lactamase (k_cat/K_m=61.4 M^-1 s ^-1) and act as weak competitive inhibitors (K_i ∼700 μM). The hydrolysis product of thioxocephalosporin, a thioacid, also inhibits the enzyme competitively with a K_i=96 μM, whereas the cyclic thioxo-piperazinedione, formed by intramolecular aminolysis of thioxocephalexin has a K_i of 29 μM.

Original language	English
Pages (from-to)	1737-1739
Number of pages	3
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	14
Issue number	7
DOIs	https://doi.org/10.1016/j.bmcl.2004.01.047
Publication status	Published - Apr 2004

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abstract = "The 8-thioxocephalosporins are poor substrates for the B. cereus metallo β-lactamase (kcat/Km=61.4 M-1 s -1) and act as weak competitive inhibitors (Ki ∼700 μM). The hydrolysis product of thioxocephalosporin, a thioacid, also inhibits the enzyme competitively with a Ki=96 μM, whereas the cyclic thioxo-piperazinedione, formed by intramolecular aminolysis of thioxocephalexin has a Ki of 29 μM.",

author = "Tsang, \{Wing Y.\} and Anupma Dhanda and Schofield, \{Christopher J.\} and Fr{\`e}re, \{Jean Marie\} and Moreno Galleni and Page, \{Michael I.\}",

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AU - Tsang, Wing Y.

AU - Dhanda, Anupma

AU - Schofield, Christopher J.

AU - Frère, Jean Marie

AU - Galleni, Moreno

AU - Page, Michael I.

PY - 2004/4

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AB - The 8-thioxocephalosporins are poor substrates for the B. cereus metallo β-lactamase (kcat/Km=61.4 M-1 s -1) and act as weak competitive inhibitors (Ki ∼700 μM). The hydrolysis product of thioxocephalosporin, a thioacid, also inhibits the enzyme competitively with a Ki=96 μM, whereas the cyclic thioxo-piperazinedione, formed by intramolecular aminolysis of thioxocephalexin has a Ki of 29 μM.

UR - https://www.scopus.com/pages/publications/1542404603

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DO - 10.1016/j.bmcl.2004.01.047

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JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 7

ER -

The inhibition of metallo-β-lactamase by thioxo-cephalosporin derivatives

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