3-Mercapto-1,2,4-triazoles and N-acylated thiosemicarbazides as metallo-beta-lactamase inhibitors

Faridoon, Hussein, Waleed M., Vella, Peter, Ul Islam, Nazar, Ollis, David L., Schenk, Gerhard and McGeary, Ross P. (2012) 3-Mercapto-1,2,4-triazoles and N-acylated thiosemicarbazides as metallo-beta-lactamase inhibitors. Bioorganic and Medicinal Chemistry Letters, 22 1: 380-386. doi:10.1016/j.bmcl.2011.10.116

Author Faridoon
Hussein, Waleed M.
Vella, Peter
Ul Islam, Nazar
Ollis, David L.
Schenk, Gerhard
McGeary, Ross P.
Title 3-Mercapto-1,2,4-triazoles and N-acylated thiosemicarbazides as metallo-beta-lactamase inhibitors
Formatted title
3-Mercapto-1,2,4-triazoles and N-acylated thiosemicarbazides as metallo-β-lactamase inhibitors
Journal name Bioorganic and Medicinal Chemistry Letters   Check publisher's open access policy
ISSN 0960-894X
Publication date 2012-01
Year available 2011
Sub-type Article (original research)
DOI 10.1016/j.bmcl.2011.10.116
Volume 22
Issue 1
Start page 380
End page 386
Total pages 7
Editor Boger, D. L.
S. Neidle
M. Shibasaki
K. Maruoka
Place of publication Oxford, England
Publisher Pergamon
Collection year 2012
Language eng
Formatted abstract
The production of β-lactamases is an effective strategy by which pathogenic bacteria can develop resistance against β-lactam antibiotics. While inhibitors of serine-β-lactamases are widely used in combination therapy with β-lactam antibiotics, there are no clinically available inhibitors of metallo-β-lactamases (MBLs), and so there is a need for the development of such inhibitors. This work describes the optimisation of a lead inhibitor previously identified by fragment screening of a compound library. We also report that thiosemicarbazide intermediates in the syntheses of these compounds are also moderately potent inhibitors of the IMP-1 MBL from Pseudomonas aeruginosa. The interactions of these inhibitors with the active site of IMP-1 were examined using in silico methods.
Keyword Antibiotic resistance
Inhibition assays
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Available online 6 November 2011

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Chemistry and Molecular Biosciences
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Citation counts: TR Web of Science Citation Count  Cited 14 times in Thomson Reuters Web of Science Article | Citations
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Created: Tue, 14 Feb 2012, 13:52:38 EST by Lucy O'Brien on behalf of School of Chemistry & Molecular Biosciences