ArticleACS infectious diseases2015
Bisthiazolidines: A Substrate-Mimicking Scaffold as an Inhibitor of the NDM-1 Carbapenemase.
Article in ACS infectious diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 111 citations in OpenAlex.
- Inhibitor Affinity Differs among Clinical Variants of IMP Metallo-ACS infectious diseases · 2025Article
- Small-molecule strategies to combat antibiotic resistance: mechanisms, modifications, and contemporary approaches.RSC advances · 2025Review
- Elucidation of critical chemical moieties of metallo-β-lactamase inhibitors and prioritisation of target metallo-β-lactamases.Journal of enzyme inhibition and medicinal chemistry · 2024Review
- The interaction of the azetidine thiazole side chain with the active site loop (ASL) 3 drives the evolution of IMP metallo-β-lactamase against tebipenem.Antimicrobial agents and chemotherapy · 2024Article
- New Delhi Metallo-Beta-Lactamase Inhibitors: A Systematic Scoping Review.Journal of clinical medicine · 2024Article
- Rational Design of Benzobisheterocycle Metallo-β-Lactamase Inhibitors: A Tricyclic Scaffold Enhances Potency against Target Enzymes.Journal of medicinal chemistry · 2024Article
- Structural role of K224 in taniborbactam inhibition of NDM-1.Antimicrobial agents and chemotherapy · 2024Article
- Review
- Identification of a Potential Inhibitor (MCULE-8777613195-0-12) of New Delhi Metallo-β-Lactamase-1 (NDM-1) Using In Silico and In Vitro Approaches.Molecules (Basel, Switzerland) · 2022Article
- Recent Developments to Cope the Antibacterial Resistance via β-Lactamase Inhibition.Molecules (Basel, Switzerland) · 2022Review
- Imipenem/Relebactam Resistance in Clinical Isolates of Extensively Drug Resistant Pseudomonas aeruginosa: Inhibitor-Resistant β-Lactamases and Their Increasing Importance.Antimicrobial agents and chemotherapy · 2022Article
- β-Lactam Antibiotics and β-Lactamase Enzymes Inhibitors, Part 2: Our Limited Resources.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Risedronate and Methotrexate Are High-Affinity Inhibitors of New Delhi Metallo-β-Lactamase-1 (NDM-1): A Drug Repurposing Approach.Molecules (Basel, Switzerland) · 2022Article
- Thioester deprotection using a biomimetic NCL approach.Frontiers in chemistry · 2022Article
- Enzyme Inhibitors: The Best Strategy to Tackle Superbug NDM-1 and Its Variants.International journal of molecular sciences · 2021Review
- 2-Mercaptomethyl Thiazolidines (MMTZs) Inhibit All Metallo-β-Lactamase Classes by Maintaining a Conserved Binding Mode.ACS infectious diseases · 2021Article
- Thiosemicarbazones exhibit inhibitory efficacy against New Delhi metallo-β-lactamase-1 (NDM-1).The Journal of antibiotics · 2021Article
- A new procedure for thioester deprotection using thioglycolic acid in both homogeneous and heterogeneous phase.Tetrahedron · 2021Article
- Metallo-β-lactamases in the Age of Multidrug Resistance: From Structure and Mechanism to Evolution, Dissemination, and Inhibitor Design.Chemical reviews · 2021Review
- Cephalosporin Prodrug Inhibitors Overcome Metallo-β-Lactamase Driven Antibiotic Resistance.Chemistry (Weinheim an der Bergstrasse, Germany) · 2021Article
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Authors and funding
13 authors at 9 institutions in 4 countries.
Funding
Abstract
Pathogenic Gram-negative bacteria resistant to almost all β-lactam antibiotics are a major public health threat. Zn(II)-dependent or metallo-β-lactamases (MBLs) produced by these bacteria inactivate most β-lactam antibiotics, including the carbapenems, which are "last line therapies" for life-threatening Gram-negative infections. NDM-1 is a carbapenemase belonging to the MBL family that is rapidly spreading worldwide. Regrettably, inhibitors of MBLs are not yet developed. Here we present the bisthiazolidine (BTZ) scaffold as a structure with some features of β-lactam substrates, which can be modified with metal-binding groups to target the MBL active site. Inspired by known interactions of MBLs with β-lactams, we designed four BTZs that behave as in vitro NDM-1 inhibitors with Ki values in the low micromolar range (from 7 ± 1 to 19 ± 3 μM). NMR spectroscopy demonstrated that they inhibit hydrolysis of imipenem in NDM-1-producing Escherichia coli. In vitro time kill cell-based assays against a variety of bacterial strains harboring blaNDM-1 including Acinetobacter baumannii show that the compounds restore the antibacterial activity of imipenem. A crystal structure of the most potent heterocycle (L-CS319) in complex with NDM-1 at 1.9 Å resolution identified both structural determinants for inhibitor binding and opportunities for further improvements in potency.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.