ArticlePloS one2013
Tricyclic GyrB/ParE (TriBE) inhibitors: a new class of broad-spectrum dual-targeting antibacterial agents.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 103 citations in OpenAlex.
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- Global health perspectives on antibacterial drug discovery and the preclinical pipeline.Nature reviews. Microbiology · 2025Review
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- Fighting Antimicrobial Resistance: Innovative Drugs in Antibacterial Research.Angewandte Chemie (International ed. in English) · 2025Review
- Antibiotic resistance mediated by gene amplifications.npj antimicrobials and resistance · 2024Review
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- Two classes of DNA gyrase inhibitors elicit distinct evolutionary trajectories toward resistance in gram-negative pathogens.npj antimicrobials and resistance · 2024Article
- Tackling the outer membrane: facilitating compound entry into Gram-negative bacterial pathogens.npj antimicrobials and resistance · 2023Review
- Design and Synthesis of Novel Antimicrobial Agents.Antibiotics (Basel, Switzerland) · 2023Review
- Developments in Non-Intercalating Bacterial Topoisomerase Inhibitors: Allosteric and ATPase Inhibitors of DNA Gyrase and Topoisomerase IV.Pharmaceuticals (Basel, Switzerland) · 2023Review
- An In-Silico Evaluation of Anthraquinones as Potential Inhibitors of DNA Gyrase B ofMicroorganisms · 2022Article
- Why Matter Matters: Fast-TrackingMolecules (Basel, Switzerland) · 2022Review
- A Novel Oral GyrB/ParE Dual Binding Inhibitor Effective against Multidrug-ResistantAntimicrobial agents and chemotherapy · 2022Article
- Activity of Tricyclic Pyrrolopyrimidine Gyrase B Inhibitor against Mycobacterium abscessus.Antimicrobial agents and chemotherapy · 2022Article
- Seasonal weather effects on offspring survival differ between reproductive stages in a long-lived neotropical seabird.Oecologia · 2022Article
- Selective DNA Gyrase Inhibitors: Multi-Target in Silico Profiling with 3D-Pharmacophores.Pharmaceuticals (Basel, Switzerland) · 2021Article
- What makes a type IIA topoisomerase a gyrase or a Topo IV?Nucleic acids research · 2021Review
- Synthesis of Computationally Designed 2,5(6)-Benzimidazole Derivatives via Pd-Catalyzed Reactions for PotentialMolecules (Basel, Switzerland) · 2021Article
- Exploring the Chemical Space of Benzothiazole-Based DNA Gyrase B Inhibitors.ACS medicinal chemistry letters · 2020Article
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Authors and funding
27 authors at 4 institutions in 1 country.
Funding
Abstract
Increasing resistance to every major class of antibiotics and a dearth of novel classes of antibacterial agents in development pipelines has created a dwindling reservoir of treatment options for serious bacterial infections. The bacterial type IIA topoisomerases, DNA gyrase and topoisomerase IV, are validated antibacterial drug targets with multiple prospective drug binding sites, including the catalytic site targeted by the fluoroquinolone antibiotics. However, growing resistance to fluoroquinolones, frequently mediated by mutations in the drug-binding site, is increasingly limiting the utility of this antibiotic class, prompting the search for other inhibitor classes that target different sites on the topoisomerase complexes. The highly conserved ATP-binding subunits of DNA gyrase (GyrB) and topoisomerase IV (ParE) have long been recognized as excellent candidates for the development of dual-targeting antibacterial agents with broad-spectrum potential. However, to date, no natural product or small molecule inhibitors targeting these sites have succeeded in the clinic, and no inhibitors of these enzymes have yet been reported with broad-spectrum antibacterial activity encompassing the majority of Gram-negative pathogens. Using structure-based drug design (SBDD), we have created a novel dual-targeting pyrimidoindole inhibitor series with exquisite potency against GyrB and ParE enzymes from a broad range of clinically important pathogens. Inhibitors from this series demonstrate potent, broad-spectrum antibacterial activity against Gram-positive and Gram-negative pathogens of clinical importance, including fluoroquinolone resistant and multidrug resistant strains. Lead compounds have been discovered with clinical potential; they are well tolerated in animals, and efficacious in Gram-negative infection models.
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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.