ArticleJournal of medicinal chemistry2006
Hybrid antibacterials. DNA polymerase-topoisomerase inhibitors.
Article in Journal of medicinal chemistry, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 63 citations in OpenAlex.
- Article
- Synthesis of Novel Ciprofloxacin-Based Hybrid Molecules toward Potent Antimalarial Activity.ACS medicinal chemistry letters · 2020Article
- Recent advances in the chemistry of 2-chloroquinoline-3-carbaldehyde and related analogs.RSC advances · 2018Review
- Comprehensive review of chemical strategies for the preparation of new aminoglycosides and their biological activities.Chemical Society reviews · 2018Review
- DNA replication proteins as potential targets for antimicrobials in drug-resistant bacterial pathogens.The Journal of antimicrobial chemotherapy · 2017Review
- Synthesis and Evaluation of Ciprofloxacin-Nitroxide Conjugates as Anti-Biofilm Agents.Molecules (Basel, Switzerland) · 2016Article
- Selective in vivo and in vitro activities of 3,3'-4-nitrobenzylidene-bis-4-hydroxycoumarin against methicillin-resistant Staphylococcus aureus by inhibition of DNA polymerase III.Scientific reports · 2015Article
- MBX-500, a hybrid antibiotic with in vitro and in vivo efficacy against toxigenic Clostridium difficile.Antimicrobial agents and chemotherapy · 2012Article
- Architecture and conservation of the bacterial DNA replication machinery, an underexploited drug target.Current drug targets · 2012Review
- In front of and behind the replication fork: bacterial type IIA topoisomerases.Cellular and molecular life sciences : CMLS · 2010Review
- Antibacterial activity and mechanism of action of a novel anilinouracil-fluoroquinolone hybrid compound.Antimicrobial agents and chemotherapy · 2007Article
- A review of patents (2011-2015) towards combating resistance to and toxicity of aminoglycosides.MedChemCommArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 2 institutions in 1 country.
Funding
Abstract
Novel Gram-positive (Gram+) antibacterial compounds consisting of a DNA polymerase IIIC (pol IIIC) inhibitor covalently connected to a topoisomerase/gyrase inhibitor are described. Specifically, 3-substituted 6-(3-ethyl-4-methylanilino)uracils (EMAUs) in which the 3-substituent is a fluoroquinolone moiety (FQ) connected by various linkers were synthesized. The resulting "AU-FQ" hybrid compounds were significantly more potent than the parent EMAU compounds as inhibitors of pol IIIC and were up to 64-fold more potent as antibacterials in vitro against Gram+ bacteria. The hybrids inhibited the FQ targets, topoisomerase IV and gyrase, with potencies similar to norfloxacin but 10-fold lower than newer agents, for example, ciprofloxacin and sparfloxacin. Representative hybrids protected mice from lethal Staphylococcus aureus infection after intravenous dosing, and one compound showed protective effect against several antibiotic-sensitive and -resistant Gram+ infections in mice. The AU-FQ hybrids are a promising new family of antibacterials for treatment of antibiotic-resistant Gram+ infections.
Indexed as
Identifiers
What OpenQuestion holds
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.