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

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 En...

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Autores principales: Avila-Bonilla, Rodolfo Gamaliel, López-Sandoval, Ángel, Soto-Sánchez, Jacqueline, Marchat, Laurence A., Rivera, Gildardo, Medina-Contreras, Oscar, Ramírez-Moreno, Esther
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271875/
https://www.ncbi.nlm.nih.gov/pubmed/35832378
http://dx.doi.org/10.3389/fcimb.2022.887647
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author Avila-Bonilla, Rodolfo Gamaliel
López-Sandoval, Ángel
Soto-Sánchez, Jacqueline
Marchat, Laurence A.
Rivera, Gildardo
Medina-Contreras, Oscar
Ramírez-Moreno, Esther
author_facet Avila-Bonilla, Rodolfo Gamaliel
López-Sandoval, Ángel
Soto-Sánchez, Jacqueline
Marchat, Laurence A.
Rivera, Gildardo
Medina-Contreras, Oscar
Ramírez-Moreno, Esther
author_sort Avila-Bonilla, Rodolfo Gamaliel
collection PubMed
description 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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spelling pubmed-92718752022-07-12 Proteomic and Functional Analysis of the Effects of Quinoxaline Derivatives on Entamoeba histolytica Avila-Bonilla, Rodolfo Gamaliel López-Sandoval, Ángel Soto-Sánchez, Jacqueline Marchat, Laurence A. Rivera, Gildardo Medina-Contreras, Oscar Ramírez-Moreno, Esther Front Cell Infect Microbiol Cellular and Infection Microbiology 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. Frontiers Media S.A. 2022-06-27 /pmc/articles/PMC9271875/ /pubmed/35832378 http://dx.doi.org/10.3389/fcimb.2022.887647 Text en Copyright © 2022 Avila-Bonilla, López-Sandoval, Soto-Sánchez, Marchat, Rivera, Medina-Contreras and Ramírez-Moreno https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Avila-Bonilla, Rodolfo Gamaliel
López-Sandoval, Ángel
Soto-Sánchez, Jacqueline
Marchat, Laurence A.
Rivera, Gildardo
Medina-Contreras, Oscar
Ramírez-Moreno, Esther
Proteomic and Functional Analysis of the Effects of Quinoxaline Derivatives on Entamoeba histolytica
title Proteomic and Functional Analysis of the Effects of Quinoxaline Derivatives on Entamoeba histolytica
title_full Proteomic and Functional Analysis of the Effects of Quinoxaline Derivatives on Entamoeba histolytica
title_fullStr Proteomic and Functional Analysis of the Effects of Quinoxaline Derivatives on Entamoeba histolytica
title_full_unstemmed Proteomic and Functional Analysis of the Effects of Quinoxaline Derivatives on Entamoeba histolytica
title_short Proteomic and Functional Analysis of the Effects of Quinoxaline Derivatives on Entamoeba histolytica
title_sort proteomic and functional analysis of the effects of quinoxaline derivatives on entamoeba histolytica
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271875/
https://www.ncbi.nlm.nih.gov/pubmed/35832378
http://dx.doi.org/10.3389/fcimb.2022.887647
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