Members of a family of N-arylsulfonyl hydrazones have been identified as novel inhibitors of IMP-1, a metallo-beta-lactamase of increasing prevalence. Structure-activity relationship studies have indicated a requirement for bulky aromatic substituents on each side of the sulfonyl hydrazone backbone for these compounds to serve as efficient inhibitors of IMP-1. Molecular modeling has provided insight into the structural basis for the anti-metallo-beta-lactamase activity exhibited by this class of compounds.
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http://dx.doi.org/10.1128/AAC.46.8.2450-2457.2002 | DOI Listing |
Microb Drug Resist
January 2025
Medical and Molecular Microbiology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.
Carbapenenemase producers, particularly the metallo-β-lactamase (MBL) types in , have emerged as an urgent threat in health care settings. MBLs require zinc at their catalytic site and can be inhibited by dimercaptosuccinic acid (DMSA), a metal chelator known for the treatment of lead and mercury intoxication. Isogenic strains of wild-type and OprD-deleted PA14, were constructed, producing the MBLs VIM-2, NDM-1, SPM-1, IMP-1, and AIM-1, or the non-MBL carbapenemases, GES-5 and KPC-2.
View Article and Find Full Text PDFAntimicrob Agents Chemother
November 2024
Servicio de Microbiología Clínica e Instituto de Investigación Biomédica A Coruña (INIBIC), Complexo Hospitalario Universitario A Coruña, A Coruña, Spain.
Antimicrob Agents Chemother
August 2024
Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Imipenemase (IMP) metallo-β-lactamases (MBLs) hydrolyze almost all available β-lactams including carbapenems and are not inhibited by any commercially available β-lactamase inhibitor. Tebipenem (TP) pivoxil is the first orally available carbapenem and possesses a unique bicyclic azetidine thiazole moiety located at the R2 position. TP has potent activity against producing extended-spectrum and/or AmpC β-lactamases.
View Article and Find Full Text PDFChemMedChem
November 2024
Biological Chemistry Group, Institute of Biology Leiden, Leiden University, Sylviusweg 72, 2333 BE, Leiden, The Netherlands.
Antibiotics, particularly the β-lactams, are a cornerstone of modern medicine. However, the rise of bacterial resistance to these agents, particularly through the actions of β-lactamases, poses a significant threat to our continued ability to effectively treat infections. Metallo-β-lactamases (MBLs) are of particular concern due to their ability to hydrolyze a wide range of β-lactam antibiotics including carbapenems.
View Article and Find Full Text PDFAntimicrob Agents Chemother
June 2024
Emerging Antibiotic Resistance, Medical and Molecular Microbiology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.
Xeruborbactam is a newly developed β-lactamase inhibitor designed for metallo-β-lactamases (MBLs). This study assessed the relative inhibitory properties of this novel inhibitor in comparison with another MBL inhibitor, namely taniborbactam (TAN), against a wide range of acquired MBL produced either in or . As observed with taniborbactam, the combination of xeruborbactam (XER) with β-lactams, namely, ceftazidime, cefepime and meropenem, led to significantly decreased MIC values for a wide range of B1-type MBL-producing , including most recombinant strains producing NDM, VIM, IMP, GIM-1, and DIM-1 enzymes.
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