ArticleThe Journal of antimicrobial chemotherapy2008
In vitro and in vivo antimycobacterial activities of ketone and amide derivatives of quinoxaline 1,4-di-N-oxide.
Article in The Journal of antimicrobial chemotherapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 56 citations in OpenAlex.
- Identifying potent inhibitors for Mycobacterium tuberculosis MabA (FabG1).Molecular diversity · 2026Article
- A Quinoxaline 1,4-Dioxide Activates DNA Repair Systems inInternational journal of molecular sciences · 2025Article
- Quinoxaline 1,4-di-Molecules (Basel, Switzerland) · 2024Article
- Expanding the chemical space of ester of quinoxaline-7-carboxylate 1,4-di-RSC medicinal chemistry · 2024Article
- Article
- Quinoxaline Moiety: A Potential Scaffold againstMolecules (Basel, Switzerland) · 2021Review
- Design, Synthesis, and Biological Evaluation of Novel Thiazolidinone-Containing Quinoxaline-1,4-di-Frontiers in chemistry · 2020Article
- Anti-Molecules (Basel, Switzerland) · 2018Article
- Targeting Phenotypically Tolerant Mycobacterium tuberculosis.Microbiology spectrum · 2017Review
- Design and synthesis of novel quinoxaline derivatives as potential candidates for treatment of multidrug-resistant and latent tuberculosis.Bioorganic & medicinal chemistry letters · 2016Article
- Combining Metabolite-Based Pharmacophores with Bayesian Machine Learning Models for Mycobacterium tuberculosis Drug Discovery.PloS one · 2015Article
- Antifungal Activity of Decyl Gallate against Several Species of Pathogenic Fungi.Evidence-based complementary and alternative medicine : eCAM · 2014Article
- Discovery and optimization of benzotriazine di-N-oxides targeting replicating and nonreplicating Mycobacterium tuberculosis.Journal of medicinal chemistry · 2012Article
- E-2-[3-(3,4-dichlorophenyl)-1-oxo-2-propenyl]-3-methylquinoxaline-1,4-dioxide: a lead antitubercular agent which alters mitochondrial respiration in rat liver.European journal of medicinal chemistry · 2010Article
- Discovery and validation of new antitubercular compounds as potential drug leads and probes.Tuberculosis (Edinburgh, Scotland) · 2009Article
- Heterocyclic-2-carboxylic acid (3-cyano-1,4-di-N-oxidequinoxalin-2-yl)amide derivatives as hits for the development of neglected disease drugs.Molecules (Basel, Switzerland) · 2009Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
objectivesTo evaluate a novel series of quinoxaline 1,4-di-N-oxides for in vitro activity against Mycobacterium tuberculosis and for efficacy in a mouse model of tuberculosis (TB).
methodsKetone and amide derivatives of quinoxaline 1,4-di-N-oxide were evaluated in in vitro and in vivo tests including: (i) activity against M. tuberculosis resistant to currently used antitubercular drugs including multidrug-resistant strains (MDR-TB resistant to isoniazid and rifampicin); (ii) activity against non-replicating persistent (NRP) bacteria; (iii) MBC; (iv) maximum tolerated dose, oral bioavailability and in vivo efficacy in mice; and (v) potential for cross-resistance with another bioreduced drug, PA-824.
resultsTen compounds were tested on single drug-resistant M. tuberculosis. In general, all compounds were active with ratios of MICs against resistant and non-resistant strains of <or=4.00. One compound, 5, was orally active in a murine model of TB, bactericidal, active against NRP bacteria and active on MDR-TB and poly drug-resistant clinical isolates (resistant to 3-5 antitubercular drugs).
conclusionsQuinoxaline 1,4-di-N-oxides represent a new class of orally active antitubercular drugs. They are likely bioreduced to an active metabolite, but the pathway of bacterial activation was different from PA-824, a bioreducible nitroimidazole in clinical trials. Compound 5 was bactericidal and active on NRP organisms indicating that activation occurred in both growing and non-replicating bacteria leading to cell death. The presence of NRP bacteria is believed to be a major factor responsible for the prolonged nature of antitubercular therapy. If the bactericidal activity and activity on non-replicating bacteria in vitro translate to in vivo conditions, quinoxaline 1,4-di-N-oxides may offer a path to shortened therapy.
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.