3-mercapto-1,2,4-triazoles and N-acylated thiosemicarbazides as metallo-β-lactamase inhibitors
| Autor: | Faridoon, Peter Vella, David L. Ollis, Nazar Ul Islam, Waleed M. Hussein, Gerhard Schenk, Ross P. McGeary |
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| Rok vydání: | 2011 |
| Předmět: |
Models
Molecular Combination therapy medicine.drug_class Stereochemistry In silico Chemistry Pharmaceutical Clinical Biochemistry Antibiotics Pharmaceutical Science Microbial Sensitivity Tests medicine.disease_cause Biochemistry Metallo β lactamase Structure-Activity Relationship Catalytic Domain Drug Discovery Drug Resistance Bacterial polycyclic compounds medicine Humans Molecular Biology biology Chemistry Pseudomonas aeruginosa Organic Chemistry Active site Pathogenic bacteria biochemical phenomena metabolism and nutrition Triazoles Anti-Bacterial Agents Semicarbazides Kinetics Models Chemical Metals Drug Design biology.protein Molecular Medicine beta-Lactamase Inhibitors |
| Zdroj: | Bioorganicmedicinal chemistry letters. 22(1) |
| ISSN: | 1464-3405 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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