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

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• 作者：Faridoon^a ; ^b ; Waleed M. Hussein^a ; ^c ; Peter Vella^a ; Nazar Ul Islam^b ; David L. Ollis^d ; Gerhard Schenk^a ; ^e ; Ross P. McGeary^a ; ^f ; ^{r.mcgeary@uq.edu.au}
• 关键词：Antibiotic resistance ; 3-Mercapto-1 ; 2 ; 4-triazoles ; Thiosemicarbazides ; Inhibition assays ; Metallo-¦Â-lactamases
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2012
• 出版时间：1 January, 2012
• 年：2012
• 卷：22
• 期：1
• 页码：380-386
• 全文大小：2304 K

文摘

The production of ¦Â-lactamases is an effective strategy by which pathogenic bacteria can develop resistance against ¦Â-lactam antibiotics. While inhibitors of serine-¦Â-lactamases are widely used in combination therapy with ¦Â-lactam antibiotics, there are no clinically available inhibitors of metallo-¦Â-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.