ArticleAntimicrobial agents and chemotherapy2008
In vitro evaluation of CBR-2092, a novel rifamycin-quinolone hybrid antibiotic: studies of the mode of action in Staphylococcus aureus.
Article in Antimicrobial agents and chemotherapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 67 citations in OpenAlex.
- Benzyl-Modified Quinolone-Aminopyrimidine Hybrids with Potent Anti-MRSA Activity and a High Barrier to Resistance.Molecules (Basel, Switzerland) · 2026Article
- Strategic re-engineering of antibiotics.Nature reviews bioengineering · 2025Article
- A Review of Antibacterial Candidates with New Modes of Action.ACS infectious diseases · 2024Review
- Synthesis of ciprofloxacin-linked 1,2,3-triazole conjugates as potent antibacterial agents using click chemistry: exploring their function as DNA gyrase inhibitorsRSC advances · 2024Article
- Antibiotics in the clinical pipeline as of December 2022.The Journal of antibiotics · 2023Review
- Bifunctional antibiotic hybrids: A review of clinical candidates.Frontiers in pharmacology · 2023Review
- Fluoroquinolones Hybrid Molecules as Promising Antibacterial Agents in the Fight against Antibacterial Resistance.Pharmaceutics · 2022Review
- Design, Synthesis, and Characterization of TNP-2198, a Dual-Targeted Rifamycin-Nitroimidazole Conjugate with Potent Activity against Microaerophilic and Anaerobic Bacterial Pathogens.Journal of medicinal chemistry · 2022Article
- Synthesis and evaluation of dual-action kanglemycin-fluoroquinolone hybrid antibiotics.Bioorganic & medicinal chemistry letters · 2022Article
- Emerging Treatment Options for Acute Bacterial Skin and Skin Structure Infections and Bloodstream Infections Caused byInfection and drug resistance · 2022Review
- Macrocycle-Antibiotic Hybrids: A Path to Clinical Candidates.Frontiers in chemistry · 2021Review
- Antibiotics in the clinical pipeline in October 2019.The Journal of antibiotics · 2020Review
- The Strategies of Pathogen-Oriented Therapy on Circumventing Antimicrobial Resistance.Research (Washington, D.C.) · 2020Review
- Synthesis, Antibacterial Activities, Mode of Action and Acute Toxicity Studies of New Oxazolidinone-Fluoroquinolone Hybrids.Molecules (Basel, Switzerland) · 2019Article
- Antibiotic Hybrids: the Next Generation of Agents and Adjuvants against Gram-Negative Pathogens?Clinical microbiology reviews · 2018Review
- Modifications of quinolones and fluoroquinolones: hybrid compounds and dual-action molecules.Monatshefte fur chemie · 2018Review
- Coumarin-benzimidazole hybrids as a potent antimicrobial agent: synthesis and biological elevation.The Journal of antibiotics · 2017Article
- A Hybrid Drug Limits Resistance by Evading the Action of the Multiple Antibiotic Resistance Pathway.Molecular biology and evolution · 2016Article
- MBX-500, a hybrid antibiotic with in vitro and in vivo efficacy against toxigenic Clostridium difficile.Antimicrobial agents and chemotherapy · 2012Article
- Antistaphylococcal activities of the new fluoroquinolone JNJ-Q2.Antimicrobial agents and chemotherapy · 2011Article
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rifamycins have proven efficacy in the treatment of persistent bacterial infections. However, the frequency with which bacteria develop resistance to rifamycin agents restricts their clinical use to antibiotic combination regimens. In a program directed toward the synthesis of rifamycins with a lower propensity to elicit resistance development, a series of compounds were prepared that covalently combine rifamycin and quinolone pharmacophores to form stable hybrid antibacterial agents. We describe mode-of-action studies with Staphylococcus aureus of CBR-2092, a novel hybrid that combines the rifamycin SV and 4H-4-oxo-quinolizine pharmacophores. In biochemical studies, CBR-2092 exhibited rifampin-like potency as an inhibitor of RNA polymerase, was an equipotent (balanced) inhibitor of DNA gyrase and DNA topoisomerase IV, and retained activity against a prevalent quinolone-resistant variant. Macromolecular biosynthesis studies confirmed that CBR-2092 has rifampin-like effects on RNA synthesis in rifampin-susceptible strains and quinolone-like effects on DNA synthesis in rifampin-resistant strains. Studies of mutant strains that exhibited reduced susceptibility to CBR-2092 further substantiated RNA polymerase as the primary cellular target of CBR-2092, with DNA gyrase and DNA topoisomerase IV being secondary and tertiary targets, respectively, in strains exhibiting preexisting rifampin resistance. In contrast to quinolone comparator agents, no strains with altered susceptibility to CBR-2092 were found to exhibit changes consistent with altered efflux properties. The combined data indicate that CBR-2092 may have potential utility in monotherapy for the treatment of persistent S. aureus infections.
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