ArticleInternational journal of molecular sciences2023
A 2.8 Å Structure of Zoliflodacin in a DNA Cleavage Complex with
Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 26 citations in OpenAlex.
- Zoliflodacin versus ceftriaxone plus azithromycin for treatment of uncomplicated urogenital gonorrhoea: an international, randomised, controlled, open-label, phase 3, non-inferiority clinical trial.Lancet (London, England) · 2026Trial
- Designing the Next Generation of Antibiotics: Structure, SAR, and Strategy in Medicinal Chemistry (2000-2025).Medicinal research reviews · 2026Review
- Design and Synthesis of Novel Morpholine-Derived Nitrogen-Rich Scaffolds as Multifunctional Anticancer and Antibacterial Agents: Biological Evaluation and Computational Studies.Pharmaceutics · 2026Article
- Nitrogen-containing FDA-approved drugs in 2025: synthesis, significance and therapeutic applications.RSC advances · 2026Review
- Halogen-Containing Drugs in 2025: A Record Year for the Therapeutic Use and Synthesis of FDA-Approved Small Molecules.Biomolecules · 2026Review
- Enzyme-DNA Interactions Affect the Catalytic Inhibition of Mycobacterial Gyrases by Antibacterial Drugs.ACS infectious diseases · 2026Article
- Gyrase and Topoisomerase IV as Antibacterial Targets for Gepotidacin and Zoliflodacin: Teaching Old Enzymes New Tricks.International journal of molecular sciences · 2026Review
- Structural interactions of BWC0977 with Klebsiella pneumoniae topoisomerase IV and biochemical basis of its broad-spectrum activity.Communications biology · 2025Article
- Structural Mechanisms of Topoisomerase-Targeting Drugs.Annual review of biochemistry · 2025Review
- Review
- Novel tetrahydronaphthalen-1-yl-phenethyl ureas: synthesis and dual antibacterial-anticancer activities.Journal of enzyme inhibition and medicinal chemistry · 2024Article
- How Do Gepotidacin and Zoliflodacin Stabilize DNA Cleavage Complexes with Bacterial Type IIA Topoisomerases? 1. Experimental Definition of Metal Binding Sites.International journal of molecular sciences · 2024Article
- A Review of Antibacterial Candidates with New Modes of Action.ACS infectious diseases · 2024Review
- Review
- Interactions between Zoliflodacin andACS infectious diseases · 2024Article
- Synthesis and biological evaluation of new naphthalimide-thiourea derivatives as potent antimicrobial agents active against multidrug-resistantRSC medicinal chemistry · 2024Article
- Gyrase and Topoisomerase IV: Recycling Old Targets for New Antibacterials to Combat Fluoroquinolone Resistance.ACS infectious diseases · 2024Review
- Interactions between Gepotidacin andACS infectious diseases · 2024Article
- Efficacy and Safety of Gepotidacin as Treatment of Uncomplicated Urogenital Gonorrhea (EAGLE-1): Design of a Randomized, Comparator-Controlled, Phase 3 Study.Infectious diseases and therapy · 2023Article
- Thiourea derivatives containing 4-arylthiazoles and d-glucose moiety: design, synthesis, antimicrobial activity evaluation, and molecular docking/dynamics simulations.RSC medicinal chemistry · 2023Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Since 2000, some thirteen quinolones and fluoroquinolones have been developed and have come to market. The quinolones, one of the most successful classes of antibacterial drugs, stabilize DNA cleavage complexes with DNA gyrase and topoisomerase IV (topo IV), the two bacterial type IIA topoisomerases. The dual targeting of gyrase and topo IV helps decrease the likelihood of resistance developing. Here, we report on a 2.8 Å X-ray crystal structure, which shows that zoliflodacin, a spiropyrimidinetrione antibiotic, binds in the same DNA cleavage site(s) as quinolones, sterically blocking DNA religation. The structure shows that zoliflodacin interacts with highly conserved residues on GyrB (and does not use the quinolone water-metal ion bridge to GyrA), suggesting it may be more difficult for bacteria to develop target mediated resistance. We show that zoliflodacin has an MIC of 4 µg/mL against
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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.