TY - JOUR
T1 - Proteomic and functional analysis of the effects of quinoxaline derivatives on entamoeba histolytica
AU - Avila-Bonilla, Rodolfo Gamaliel
AU - López-Sandoval, Ángel
AU - Soto-Sánchez, Jacqueline
AU - Marchat, Laurence A.
AU - Rivera, Gildardo
AU - Medina-Contreras, Oscar
AU - Ramírez-Moreno, Esther
N1 - Funding Information:
This work was supported by the Secretaría de Investigación y Posgrado, Instituto Politécnico Nacional (SIP-IPN)-Mexico (projects 20200335, 20211108). RGAB received financial support through the scholarship 285467 granted by SEP/CONACYT-Mexico. ER-M, LM and GR received supports from COFAA-IPN, EDI-IPN and SNI-CONACyT. AL-S received a BEIFI-IPN support and CONACYT fellowship (CVU1008704).
Publisher Copyright:
Copyright © 2022 Avila-Bonilla, López-Sandoval, Soto-Sánchez, Marchat, Rivera, Medina-Contreras and Ramírez-Moreno.
PY - 2022/6/27
Y1 - 2022/6/27
N2 - 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.
AB - 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.
KW - animals
KW - entamoeba histolytica
KW - humans
KW - proteomics
KW - pyrazines
KW - quinoxalines
KW - reactive oxygen species
KW - Thioredoxin-Disulfide Reductase
KW - trophozoites
KW - metabolism
KW - pharmacology
U2 - 10.3389/fcimb.2022.887647
DO - 10.3389/fcimb.2022.887647
M3 - Article
C2 - 35832378
SN - 2235-2988
VL - 12
JO - Frontiers in Cellular and Infection Microbiology
JF - Frontiers in Cellular and Infection Microbiology
M1 - 887647
ER -