Selective activity against Mycobacterium tuberculosis of new quinoxaline 1,4-di-N-oxides

Vicente, Esther; Pérez‐Silanes, Silvia; Lima, Lı́dia Moreira; Ancizu, Saioa; Burguete, Asunción; Solano, Beatriz; Villar, Raquel; Aldana, Ignacio; Monge, Antonio

doi:10.1016/j.bmc.2008.10.086

Cited by 101 publications

(67 citation statements)

References 19 publications

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“…In particular, N-oxide-containing quinoxaline derivatives were shown to reduce the growth of Mycobacterium tuberculosis both in vitro and in vivo (43,50,52,53) and also that of the human malaria parasite Plasmodium falciparum (51). In the present study, we have found that a quinoxaline-containing compound without 1,4-N-oxides is also effective against an apicomplexan parasite, in this case Toxoplasma gondii.…”

Section: Discussionsupporting

confidence: 53%

A Novel Benzodioxole-Containing Inhibitor of Toxoplasma gondii Growth Alters the Parasite Cell Cycle

Kamau

Meehan

Lavine

et al. 2011

Antimicrob Agents Chemother

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Toxoplasma gondii is an obligate intracellular parasite that can cause disease in the developing fetus and in immunocompromised humans. Infections can last for the life of the individual, and to date there are no drugs that eliminate the chronic cyst stages that are characteristic of this parasite. In an effort to identify new chemical scaffolds that could form the basis for new therapeutics, we carried out a chemoinformatic screen for compounds that had the potential to interact with members of a superfamily of parasite-secreted kinases and assayed them for growth inhibition in vitro. Of 17 candidate compounds, we identified one with potent antiparasitic activity. The compound has a 50% inhibitory concentration (IC 50 ) of ϳ2 nM, and structurefunction analyses implicate the benzodioxole moiety in its action. The compound does not appear to be cytotoxic to host cells. Using microarray analyses of both parasites and host cells treated with the compound, we found that the levels of very few host cell transcripts are altered by the compound, while a large number of parasite transcripts have a different abundance after compound treatment. Gene ontology analyses of parasite transcripts with a different abundance revealed an enrichment of cell cycle-related genes, suggesting that the compound alters progression of the parasite through the cell cycle. Assaying the nuclear content of treated parasites demonstrated that compound treatment significantly increased the percentage of parasites in the S/M phase of the cell cycle compared to controls. This compound and its analogs represent a novel scaffold with antiparasitic activity.

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Section: Discussionsupporting

confidence: 53%

A Novel Benzodioxole-Containing Inhibitor of Toxoplasma gondii Growth Alters the Parasite Cell Cycle

Kamau

Meehan

Lavine

et al. 2011

Antimicrob Agents Chemother

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“…Furthermore, 45% of the evaluated derivatives showed a good in vitro activity/toxicity ratio. The most active compound was 7-methyl-3-(4'-fluoro) phenylquinoxaline-2-carbonitrile 1, 4-di-N-oxide (43) (MIC <0.2 μg/mL and SI >500) [136]. In conclusion, the potency, low cytotoxicity and selectivity of these compounds make them valid lead compounds for synthesizing new anti-TB agents.…”

Section: Quinoline and Quinoxaline Derivativesmentioning

confidence: 94%

Role of quinolones and quinoxaline derivatives in the advancement of treatment of tuberculosis

Asif

2015

IJSW

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The need of new chemotherapeutic drugs to improve tuberculosis control and treatment particularly against multidrugresistant (MDR) and extensively drug resistant (XDR) strains of Mycobacterium. The atitubercular drugs are used in current chemotherapy have different chemical moieties. In this review, we provide an overview of the quinolone drugs as an antitubercular drug. Generally quinolone drugs are mainly used against many gram-positive and gram-negative bacterial infections including resistance strains also. Various quinolones are being used to control and treatment of tubercular infections including MDR, XDR and atypical Mycobacterium strains. Fluoroquinolones are an important quinolones, especially for strains that are resistant to first-line agents.

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“…The quinoxaline compounds have activity on non--replicating bacteria, which could lead to shorter anti--TB activity. 21 A new derivative of quinolone denominated ER--2 (13) reported to inhibit gyrase supercoiling in M. tuberculosis similar to Ciprofloxacin with a MIC90 of 0.5μg/mL. 22 …”

Section: Non--fluoroquinolonesmentioning

confidence: 99%

Antitubercular drugs: advances in nitrogen containing heterocyclic compounds and some other derivatives

Asif

2014

J PHARM CHEM

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Tuberculosis (TB) caused by Mycobacterium tuberculosis is an infectious disease. Control of TB is complicated by difficulties in the long--course chemotherapy treatment, the inability to eliminate latent microbes, and the increasing emergence of Multidrug Resistant (MDR) strains of M. tuberculosis. New anti--TB drugs are urgently needed, including developments of short--term treatments to minimize the emergence of drug resistance and new drugs to treat multidrug resistant tuberculosis and to eliminate the latent microbes. Many new structural anti--TB agents exhibited promising activities against susceptible and resistant strains of M. tuberculosis. The diarylquinoline with superior anti--tuberculotic activity and encouraging results of nitroimidazopyrans and oxazolidinones have generated considerable excitement.

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Selective activity against Mycobacterium tuberculosis of new quinoxaline 1,4-di-N-oxides

Cited by 101 publications

References 19 publications

A Novel Benzodioxole-Containing Inhibitor of Toxoplasma gondii Growth Alters the Parasite Cell Cycle

A Novel Benzodioxole-Containing Inhibitor of Toxoplasma gondii Growth Alters the Parasite Cell Cycle

Role of quinolones and quinoxaline derivatives in the advancement of treatment of tuberculosis

Antitubercular drugs: advances in nitrogen containing heterocyclic compounds and some other derivatives

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