QSAR analysis for quinoxaline-2-carboxylate 1,4-di-N-oxides as anti-mycobacterial agents

Vicente, Esther; Duchowicz, Pablo R.; Castro, Eduardo A.; Monge, Antonio

doi:10.1016/j.jmgm.2009.03.004

Cited by 32 publications

(17 citation statements)

References 35 publications

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“…3), was the most potent, decreasing parasite growth by 96% Ϯ 0.14% (P Ͻ 0.001 compared to vehicle control). Dose curves showed that the 50% inhibitory concentration (IC 50 ) of F1792-0016 is 2.1 Ϯ 1.8 nM (Fig. 5A), but there is also a reproducible plateau between 10 and 100 nM, suggesting that this compound may have multiple binding sites and/or targets with different inhibitory concentrations.…”

Section: F1792-0016 Inhibits Toxoplasma Growth In Vitromentioning

confidence: 99%

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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: F1792-0016 Inhibits Toxoplasma Growth In Vitromentioning

confidence: 99%

“…The monolayers were then washed 3 times in PBS and postfixed in 1% osmium tetroxide in 1% potassium ferricyanide for 1 h at 4°C. Monolayers were washed 3 times in PBS and then dehydrated in a graded ethanol series (30,50,70, and 90%). The final dehydration step was done 3 times in 100% ethanol with 15-min incubations between changes.…”

mentioning

confidence: 99%

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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“…Hence, the present study is aimed to establish the QSAR between experimental antiplasmodial activity and structure electronic or descriptors, which may focus on the molecular structures of the compounds. In last decades, QSAR has been applied in many areas enabling to prevent time consuming and cost during the analysis of biological activities of interest [12]. The main hypothesis involved in any QSAR is the assumption that the variation of the behaviour of chemical compounds, as expressed by any experimentally measured biological property, can be correlated with numerical entities related to some aspect of the chemical structure termed molecular descriptors [12,13].…”

Section: Introductionmentioning

confidence: 99%

“…In last decades, QSAR has been applied in many areas enabling to prevent time consuming and cost during the analysis of biological activities of interest [12]. The main hypothesis involved in any QSAR is the assumption that the variation of the behaviour of chemical compounds, as expressed by any experimentally measured biological property, can be correlated with numerical entities related to some aspect of the chemical structure termed molecular descriptors [12,13]. The descriptors are generally used to describe different characteristics of the chemical structure in order to yield information about the activity being studied.…”

Section: Introductionmentioning

confidence: 99%

“…The cyclic ring system of flavone derivatives compounds with multiple applications which have been the subject of great interest because of their biological activities. The four substituents (R4, R6, R7 and R4') of flavone derivatives (Table-1) has emerged in its usage as a core structure in the diversified therapeutically applications [11,12]. Previous QSAR analysis has been reported using electronic descriptor producing by PM3 calculation using 16 flavone series compound.…”

Section: Introductionmentioning

confidence: 99%

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A QSAR Analysis of Flavone Derivatives of Antimalarial Compounds Based on PM3 Semi-Empirical Method

Hadanu¹

2017

Asian J. Chem.

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The study of flavone as antimalarial compounds have been carried out by as reported earlier, but studies of QSAR for modeling flavone derivatives as new drugs to replace antimalarials that have been resistant not been carried out. The descriptors of QSAR were calculated using PM3 semi-empirical method. The best model of QSAR was determined by MLR approach. Based on the best equation of QSAR models have been designed several new antimalarial compounds that are predicted to have a higher antimalarial activity than the flavone compounds. The best equation of QSAR models have been designed for 39 compounds of flavone derivatives and only 28 compounds of flavone derivatives that can be recommended to be synthesized or isolated from natural materials in the laboratory, i.e. 17-29, 32-33, 35 and 40-51 who have IC50 values as much as 1.151-1.751 µM.

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Asymmetric Synthesis of Quaternary β‐Perfluorophenyl‐β‐amino‐indolin‐2‐ones

et al. 2017

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Reported herein is a design and synthesis of N‐tert‐butylsulfinyl‐(perfluoro)benzaldimine, and a study of its reactivity and stereocontrolling properties in Mannich addition reactions with indolinone derived tertiary enolates generated in situ. The corresponding products, quaternary β‐perfluorophenyl‐β‐amino‐indolin‐2‐ones, were obtained with good to excellent yields and diastereoselectivity, underscoring the exciting synthetic potential of this newly introduced pentafluorophenyl‐containing chiral imine.

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QSAR analysis for quinoxaline-2-carboxylate 1,4-di-N-oxides as anti-mycobacterial agents

Cited by 32 publications

References 35 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

A QSAR Analysis of Flavone Derivatives of Antimalarial Compounds Based on PM3 Semi-Empirical Method

Asymmetric Synthesis of Quaternary β‐Perfluorophenyl‐β‐amino‐indolin‐2‐ones

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