ArticleAntimicrobial agents and chemotherapy2014
NBTI 5463 is a novel bacterial type II topoisomerase inhibitor with activity against gram-negative bacteria and in vivo efficacy.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 45 citations in OpenAlex.
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- Gyrase and Topoisomerase IV: Recycling Old Targets for New Antibacterials to Combat Fluoroquinolone Resistance.ACS infectious diseases · 2024Review
- Novel Indane-Containing NBTIs with Potent Anti-Gram-Negative Activity and Minimal hERG Inhibition.ACS medicinal chemistry letters · 2023Article
- Discovery of a Series of Indane-Containing NBTIs with Activity against Multidrug-Resistant Gram-Negative Pathogens.ACS medicinal chemistry letters · 2023Article
- A CcdB toxin-derived peptide acts as a broad-spectrum antibacterial therapeutic in infected mice.EMBO reports · 2023Article
- Why Matter Matters: Fast-TrackingMolecules (Basel, Switzerland) · 2022Review
- Spiropyrimidinetriones: a Class of DNA Gyrase Inhibitors with Activity against Mycobacterium tuberculosis and without Cross-Resistance to Fluoroquinolones.Antimicrobial agents and chemotherapy · 2022Article
- Antibacterial Activity of the Novel Drug Gepotidacin againstAntibiotics (Basel, Switzerland) · 2022Article
- A Mycobacterium tuberculosis NBTI DNA Gyrase Inhibitor Is Active against Mycobacterium abscessus.Antimicrobial agents and chemotherapy · 2021Article
- Bioactive Potential of 2-Methoxy-4-vinylphenol and Benzofuran fromFoods (Basel, Switzerland) · 2020Article
- Article
- Bimodal Actions of a Naphthyridone/Aminopiperidine-Based Antibacterial That Targets Gyrase and Topoisomerase IV.Biochemistry · 2019Article
- Rapid Evolution of Reduced Susceptibility against a Balanced Dual-Targeting Antibiotic through Stepping-Stone Mutations.Antimicrobial agents and chemotherapy · 2019Article
- Mechanistic and Structural Basis for the Actions of the Antibacterial Gepotidacin against Staphylococcus aureus Gyrase.ACS infectious diseases · 2019Article
- Mechanism of Action of Mycobacterium tuberculosis Gyrase Inhibitors: A Novel Class of Gyrase Poisons.ACS infectious diseases · 2018Article
- The Macromolecular Machines that Duplicate the Escherichia coli Chromosome as Targets for Drug Discovery.Antibiotics (Basel, Switzerland) · 2018Review
- Article
- Gepotidacin (GSK2140944)Antimicrobial agents and chemotherapy · 2017Article
- DNA replication proteins as potential targets for antimicrobials in drug-resistant bacterial pathogens.The Journal of antimicrobial chemotherapy · 2017Review
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The need for new antibiotics that address serious Gram-negative infections is well recognized. Our efforts with a series of novel bacterial type II topoisomerase inhibitors (NBTIs) led to the discovery of NBTI 5463, an agent with improved activity over other NBTIs against Gram-negative bacteria, in particular against Pseudomonas aeruginosa (F. Reck, D. E. Ehmann, T. J. Dougherty, J. V. Newman, S. Hopkins, G. Stone, N. Agrawal, P. Ciaccio, J. McNulty, H. Barthlow, J. O'Donnell, K. Goteti, J. Breen, J. Comita-Prevoir, M. Cornebise, M. Cronin, C. J. Eyermann, B. Geng, G. R. Carr, L. Pandarinathan, X. Tang, A. Cottone, L. Zhao, N. Bezdenejnih-Snyder, submitted for publication). In the present work, NBTI 5463 demonstrated promising activity against a broad range of Gram-negative pathogens. In contrast to fluoroquinolones, the compound did not form a double-strand DNA cleavable complex with Escherichia coli DNA gyrase and DNA, but it was a potent inhibitor of both DNA gyrase and E. coli topoisomerase IV catalytic activities. In studies with P. aeruginosa, NBTI 5463 was bactericidal. Resistant mutants arose at a low rate, and the mutations were found exclusively in the nfxB gene, a regulator of the MexCD-OprJ efflux system. Levofloxacin-selected resistance mutations in GyrA did not result in decreased susceptibility to NBTI 5463. Animal infection studies demonstrated that NBTI 5463 was efficacious in mouse models of lung, thigh, and ascending urinary tract infections.
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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.