Synthesis of quinoxaline 1,4-di-N-oxide derivatives on solid support using room temperature and microwave-assisted solvent-free procedures

Gómez-Caro, Lilia Citlalli; Sánchez-Sánchez, Mario; Bocanegra-García, Virgilio; Rivera, Gildardo; Monge, Antonio

doi:10.1590/s0100-40422011000700008

Cited by 15 publications

(7 citation statements)

References 22 publications

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“…Propyl and isopropyl quinoxaline-7-carboxylate 1,4-di- N -oxide derivatives were synthetized as described by Gomez-Caro et al [ 30 ]. The compounds were characterized by infrared (IR), nuclear magnetic resonance (NMR), and elemental analysis.…”

Section: Methodsmentioning

confidence: 99%

Trypanocidal Activity of Quinoxaline 1,4 Di-N-oxide Derivatives as Trypanothione Reductase Inhibitors

et al. 2017

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Chagas disease or American trypanosomiasis is a worldwide public health problem. In this work, we evaluated 26 new propyl and isopropyl quinoxaline-7-carboxylate 1,4-di-N-oxide derivatives as potential trypanocidal agents. Additionally, molecular docking and enzymatic assays on trypanothione reductase (TR) were performed to provide a basis for their potential mechanism of action. Seven compounds showed better trypanocidal activity on epimastigotes than the reference drugs, and only four displayed activity on trypomastigotes; T-085 was the lead compound with an IC50 = 59.9 and 73.02 µM on NINOA and INC-5 strain, respectively. An in silico analysis proposed compound T-085 as a potential TR inhibitor with better affinity than the natural substrate. Enzymatic analysis revealed that T-085 inhibits parasite TR non-competitively. Compound T-085 carries a carbonyl, a CF3, and an isopropyl carboxylate group at 2-, 3- and 7-position, respectively. These results suggest the chemical structure of this compound as a good starting point for the design and synthesis of novel trypanocidal derivatives with higher TR inhibitory potency and lower toxicity.

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Section: Methodsmentioning

confidence: 99%

Trypanocidal Activity of Quinoxaline 1,4 Di-N-oxide Derivatives as Trypanothione Reductase Inhibitors

et al. 2017

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“…Methyl (m-), ethyl (e-), isopropyl (i-), and n-propyl (np-) EQX-NO derivatives were obtained (see Supplementary material) (18) and evaluated in vitro against T. vaginalis. Table I shows their trichomonicidal activity.…”

Section: Resultsmentioning

confidence: 99%

“…All EQX-NO derivatives were synthesized using the method reported by Gomez-Caro et al (18). All molecules were identified by IR spectroscopy, 1 H NMR and elemental analysis of C, H and N (see Table SI, Supplementary material), as in previous research (14,15,17,18).…”

Section: Synthesesmentioning

confidence: 99%

Esters of quinoxaline-7-carboxylate-1,4-di-N-oxide as Trichomonas vaginalis triosephosphate isomerase inhibitors

et al. 2020

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Trichomoniasis is a public health problem worldwide. Trichomoniasis treatment consists of the use of nitroimidazole derivatives; however, therapeutic ineffectiveness occurs in 5 to 20 % of the cases. Therefore, it is essential to propose new pharmacological agents against this disease. In this work, esters of quinoxaline-7-carboxylate-1,4-di-N-oxide (EQX-NO) were evaluated in in vitro assays as novel trichomonicidal agents. Additionally, an in vitro enzyme assay and molecular docking analysis against triosephosphate isomerase of Trichomonas vaginalis to confirm their mechanism of action were performed. Ethyl (compound 12) and n-propyl (compound 37) esters of quinoxaline-7-carboxy-late-1,4-di-N-oxide derivatives showed trichomonicidal activity comparable to nitazoxanide, whereas five methyl (compounds 5, 15, 19, 20 and 22), four isopropyl (compounds 28, 29, 30 and 34), three ethyl (compounds 4, 13 and 23) and one npropyl (compound 35) ester derivatives displayed activity comparable to albendazole. Compounds 6 and 20 decreased 100 % of the enzyme activity of recombinant protein triosephosphate isomerase.

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“…Quinoxaline derivatives T-001 (Methyl 2-acetyl-3-methyl-quinoxaline-7-carboxylate 1,4-di-N-oxide) and T-017 (Ethyl 2-benzoyl-3-methylquinoxaline-7-carboxylate 1,4-di-N-oxide) were synthesized as described ( Gómez-Caro et al., 2011 ). Stock solutions were prepared in DMSO (the concentration used in the experiments did not exceed 0.01%) and each compound was prepared at a final concentration of 1 mg/mL.…”

Section: Methodsmentioning

confidence: 99%

Proteomic and Functional Analysis of the Effects of Quinoxaline Derivatives on Entamoeba histolytica

Avila-Bonilla

López-Sandoval

Soto‐Sanchez

et al. 2022

Front. Cell. Infect. Microbiol.

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Quinoxalines are heterocyclic compounds that contain a benzene ring and a pyrazine ring. The oxidation of both nitrogen of the pyrazine ring results in quinoxaline derivatives (QdNO), which exhibit a variety of biological properties, including antiparasitic activity. However, its activity against Entamoeba histolytica, the protozoan that causes human amebiasis, is poorly understood. Recently, our group reported that various QdNOs produce morphological changes in E. histolytica trophozoites, increase reactive oxygen species, and inhibit thioredoxin reductase activity. Notably, T-001 and T-017 derivatives were among the QdNOs with the best activity. In order to contribute to the characterization of the antiamebic effect of QdNOs, in this work we analyzed the proteomic profile of E. histolytica trophozoites treated with the QdNOs T-001 and T-017, and the results were correlated with functional assays. A total number of 163 deregulated proteins were found in trophozoites treated with T-001, and 131 in those treated with T-017. A set of 21 overexpressed and 24 under-expressed proteins was identified, which were mainly related to cytoskeleton and intracellular traffic, nucleic acid transcription, translation and binding, and redox homeostasis. Furthermore, T-001 and T-017 modified the virulence of trophozoites, since they altered their erythrophagocytosis, migration, adhesion and cytolytic capacity. Our results show that in addition to alter reactive oxygen species, and thioredoxin reductase activity, T-001 and T-017 affect essential functions related to the actin cytoskeleton, which eventually affects E. histolytica virulence and survival.

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Synthesis of quinoxaline 1,4-di-N-oxide derivatives on solid support using room temperature and microwave-assisted solvent-free procedures

Cited by 15 publications

References 22 publications

Trypanocidal Activity of Quinoxaline 1,4 Di-N-oxide Derivatives as Trypanothione Reductase Inhibitors

Trypanocidal Activity of Quinoxaline 1,4 Di-N-oxide Derivatives as Trypanothione Reductase Inhibitors

Esters of quinoxaline-7-carboxylate-1,4-di-N-oxide as Trichomonas vaginalis triosephosphate isomerase inhibitors

Proteomic and Functional Analysis of the Effects of Quinoxaline Derivatives on Entamoeba histolytica

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