ArticleACS chemical biology2014
Bypassing fluoroquinolone resistance with quinazolinediones: studies of drug-gyrase-DNA complexes having implications for drug design.
Article in ACS chemical biology, 2014. 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, 44 citations in OpenAlex.
- Chinese advances in understanding and managing genitourinary tract infections caused by Mycoplasma genitalium, Mycoplasma hominis, and Ureaplasma urealyticum.Archives of microbiology · 2024Review
- Target-Mediated Fluoroquinolone Resistance inACS infectious diseases · 2024Article
- Dynamic Intramolecular Cap for Preserving Metallodrug Integrity─A Case of Catalytic Fluoroquinolones.Journal of medicinal chemistry · 2022Article
- Novel and Structurally Diversified Bacterial DNA Gyrase Inhibitors Discovered through a Fluorescence-Based High-Throughput Screening Assay.ACS pharmacology & translational science · 2022Article
- Rational design, synthesis and testing of novel tricyclic topoisomerase inhibitors for the treatment of bacterial infections part 2.RSC medicinal chemistry · 2020Article
- Quinolones: Mechanism, Lethality and Their Contributions to Antibiotic Resistance.Molecules (Basel, Switzerland) · 2020Review
- Magnetic covalent organic frameworks with core-shell structure as sorbents for solid phase extraction of fluoroquinolones, and their quantitation by HPLC.Mikrochimica acta · 2019Article
- Article
- Characterization ofIranian journal of microbiology · 2018Article
- A new class of antibacterials, the imidazopyrazinones, reveal structural transitions involved in DNA gyrase poisoning and mechanisms of resistance.Nucleic acids research · 2018Article
- Suppression of Reactive Oxygen Species Accumulation Accounts for Paradoxical Bacterial Survival at High Quinolone Concentration.Antimicrobial agents and chemotherapy · 2018Article
- Analytical profiling of mutations in quinolone resistance determining region of gyrA gene among UPEC.PloS one · 2018Article
- Fluoroquinolones as imaging agents for bacterial infection.Dalton transactions (Cambridge, England : 2003) · 2017Review
- Interactions between Quinolones and Bacillus anthracis Gyrase and the Basis of Drug Resistance.Biochemistry · 2017Article
- Exploring the active site of the Streptococcus pneumoniae topoisomerase IV-DNA cleavage complex with novel 7,8-bridged fluoroquinolones.Open biology · 2016Article
- Suppression of gyrase-mediated resistance by C7 aryl fluoroquinolones.Nucleic acids research · 2016Article
- Structure of a quinolone-stabilized cleavage complex of topoisomerase IV from Klebsiella pneumoniae and comparison with a related Streptococcus pneumoniae complex.Acta crystallographica. Section D, Structural biology · 2016Article
- Crystal structure and stability of gyrase-fluoroquinolone cleaved complexes from Mycobacterium tuberculosis.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- A "Double-Edged" Scaffold: Antitumor Power within the Antibacterial Quinolone.Current medicinal chemistry · 2016Review
- Structural basis of DNA gyrase inhibition by antibacterial QPT-1, anticancer drug etoposide and moxifloxacin.Nature communications · 2015Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Widespread fluoroquinolone resistance has drawn attention to quinazolinediones (diones), fluoroquinolone-like topoisomerase poisons that are unaffected by common quinolone-resistance mutations. To better understand differences between quinolones and diones, we examined their impact on the formation of cleaved complexes (drug-topoisomerase-DNA complexes in which the DNA moiety is broken) with gyrase, one of two bacterial targets of the drugs. Formation of cleaved complexes, measured by linearization of a circular DNA substrate, required lower concentrations of quinolone than dione. The reverse reaction, detected as resealing of DNA breaks in cleaved complexes, required higher temperatures and EDTA concentrations for quinolones than diones. The greater stability of quinolone-containing complexes was attributed to the unique ability of the quinolone C3/C4 keto acid to complex with magnesium and form a previously described drug-magnesium-water bridge with GyrA-Ser83 and GyrA-Asp87. A nearby substitution in GyrA (G81C) reduced activity differences between quinolone and dione, indicating that resistance due to this variation derives from perturbation of the magnesium-water bridge. To increase dione activity, we examined a relatively small, flexible C-7-3-(aminomethyl)pyrrolidinyl substituent, which is distal to the bridging C3/C4 keto acid substituent of quinolones. The 3-(aminomethyl)pyrrolidinyl group at position C-7 was capable of forming binding interactions with GyrB-Glu466, as indicated by inspection of crystal structures, computer-aided docking, and measurement of cleaved-complex formation with mutant and wild-type GyrB proteins. Thus, modification of dione C-7 substituents constitutes a strategy for obtaining compounds active against common quinolone-resistant mutants.
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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.