ArticleAntimicrobial agents and chemotherapy2007
Antibacterial activity and mechanism of action of a novel anilinouracil-fluoroquinolone hybrid compound.
Article in Antimicrobial agents and chemotherapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 64 citations in OpenAlex.
- Designing Antibiotics with Inherent Resistance to Efflux as a Strategy to Revive Discovery against Multidrug-Resistant Pathogens.Journal of medicinal chemistry · 2026Article
- Vistas in the domain of 3-acetyl-4-hydroxy-2-quinolinone derivatives (AHQ) and their applications.RSC advances · 2025Review
- Fighting Antimicrobial Resistance: Innovative Drugs in Antibacterial Research.Angewandte Chemie (International ed. in English) · 2025Review
- Investigating N-arylpyrimidinamine (NAPA) compounds as early-stage inhibitors against human cytomegalovirus.Antiviral research · 2023Article
- Novel Antibiotics Targeting Bacterial Replicative DNA Polymerases.Antibiotics (Basel, Switzerland) · 2020Review
- Watching DNA Replication Inhibitors in Action: Exploiting Time-Lapse Microfluidic Microscopy as a Tool for Target-Drug Interaction Studies inAntimicrobial agents and chemotherapy · 2019Article
- Modifications of quinolones and fluoroquinolones: hybrid compounds and dual-action molecules.Monatshefte fur chemie · 2018Review
- DNA replication proteins as potential targets for antimicrobials in drug-resistant bacterial pathogens.The Journal of antimicrobial chemotherapy · 2017Review
- A Review of Experimental and Off-Label Therapies for Clostridium difficile Infection.Infectious diseases and therapy · 2017Review
- Targeting DNA Replication and Repair for the Development of Novel Therapeutics against Tuberculosis.Frontiers in molecular biosciences · 2017Review
- DNA Targeting as a Likely Mechanism Underlying the Antibacterial Activity of Synthetic Bis-Indole Antibiotics.Antimicrobial agents and chemotherapy · 2016Article
- Article
- Synthesis and antifungal evaluation of head-to-head and head-to-tail bisamidine compounds.Bioorganic & medicinal chemistry · 2015Article
- Structure-activity relationships of a novel pyranopyridine series of Gram-negative bacterial efflux pump inhibitors.Bioorganic & medicinal chemistry · 2015Article
- Identification of potential drug targets by subtractive genome analysis of Escherichia coli O157:H7: an in silico approach.Advances and applications in bioinformatics and chemistry : AABC · 2015Article
- Structure-activity exploration of a small-molecule Lipid II inhibitor.Drug design, development and therapy · 2015Article
- Characterization of a novel pyranopyridine inhibitor of the AcrAB efflux pump of Escherichia coli.Antimicrobial agents and chemotherapy · 2014Article
- 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
- DNA polymerase III α subunit from Mycobacterium tuberculosis H37Rv: Homology modeling and molecular docking of its inhibitor.Bioinformation · 2011Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
The anilinouracils (AUs) such as 6-(3-ethyl-4-methylanilino)uracil (EMAU) are a novel class of gram-positive, selective, bactericidal antibacterials which inhibit pol IIIC, the gram-positive-specific replicative DNA polymerase. We have linked various fluoroquinolones (FQs) to the N-3 position of EMAU to generate a variety of AU-FQ "hybrids" offering the potential for targeting two distinct steps in DNA replication. In this study, the properties of a hybrid, "251D," were compared with those of representative AUs and FQs in a variety of in vitro assays, including pol IIIC and topoisomerase/gyrase enzyme assays, antibacterial, bactericidal, and mammalian cytotoxicity assays. Compound 251D potently inhibited pol IIIC and topoisomerase/gyrase, displayed gram-positive antibacterial potency at least 15 times that of the corresponding AU compound, and as expected, acted selectively on bacterial DNA synthesis. Compound 251D was active against a broad panel of antibiotic-resistant gram-positive pathogens as well as several gram-negative organisms and was also active against both AU- and FQ-resistant gram-positive organisms, demonstrating its capacity for attacking both of its potential targets in the bacterium. 251D also was bactericidal for gram-positive organisms and lacked toxicity in vitro. Although we obtained strains of Staphylococcus aureus resistant to the individual parent compounds, spontaneous resistance to 251D was not observed. We obtained 251D resistance in multiple-passage experiments, but resistance developed at a pace comparable to those for the parent compounds. This class of AU-FQ hybrids provides a promising new pharmacophore with an unusual dual mechanism of action and potent activity against antibiotic-sensitive and -resistant gram-positive pathogens.
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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.