N-arylsulfonyl hydrazones as inhibitors of IMP-1 metallo-beta-lactamase.

Antimicrob Agents Chemother

Department of Chemistry, University of Waterloo, 200 University Avenue W., Waterloo, Ontario N2L 3G1, Canada.

Published: August 2002

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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC127367PMC
http://dx.doi.org/10.1128/AAC.46.8.2450-2457.2002DOI Listing

Publication Analysis

Top Keywords

inhibitors imp-1
12
n-arylsulfonyl hydrazones
8
imp-1 metallo-beta-lactamase
8
hydrazones inhibitors
4
metallo-beta-lactamase members
4
members family
4
family n-arylsulfonyl
4
hydrazones identified
4
identified novel
4
novel inhibitors
4

Similar Publications

Activity of Dimercaptosuccinic Acid in Combination with Carbapenems Against Carbapenem-Resistant .

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 PDF
Article Synopsis
  • The study investigated the efficacy and resistance mechanisms of cefiderocol and new β-lactam/β-lactamase inhibitor combinations against strains of Enterobacterales producing multiple carbapenemases, specifically focusing on clinical samples from Spanish hospitals collected between 2017 and 2022.
  • The analysis involved 57 isolates, where minimum inhibitory concentration (MIC) values were determined for various antibiotics, and whole-genome sequencing was utilized to identify genetic resistance factors.
  • Ceftazidime/avibactam, imipenem/relebactam, and meropenem/vaborbactam showed the least activity, while combinations like aztreonam/avibactam and cefepime/zidebactam were
View Article and Find Full Text PDF

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 PDF

Synthesis and Evaluation of Carbapenem/Metallo-β-Lactamase Inhibitor Conjugates.

ChemMedChem

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 PDF

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.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!