Phosphoenolpyruvate carboxykinase from T. cruzi magnetic beads affinity-based screening assays on crude plant extracts from Brazilian Cerrado.

Autor: do Amaral BS; Instituto Federal de Educação, Ciência e Tecnologia de São Paulo, Campus Pirituba, 05110-000, São Paulo, SP, Brazil; Departamento de Química, Universidade Federal de São Carlos, Rodovia Washington Luís, km 235, 13565-905, São Carlos, SP, Brazil., da Silva LRG; Departamento de Química, Universidade Federal de São Carlos, Rodovia Washington Luís, km 235, 13565-905, São Carlos, SP, Brazil; Instituto de Química, Programa de Pós-Graduação em Química, Universidade Federal Fluminense, Niterói, RJ, Brazil., Valverde AL; Instituto de Química, Programa de Pós-Graduação em Química, Universidade Federal Fluminense, Niterói, RJ, Brazil., de Sousa LRF; Unidade Acadêmica Especial de Química, Universidade Federal de Goiás, Regional Catalão, 75704-020, Catalão, GO, Brazil., Severino RP; Unidade Acadêmica Especial de Química, Universidade Federal de Goiás, Regional Catalão, 75704-020, Catalão, GO, Brazil., de Souza DHF; Departamento de Química, Universidade Federal de São Carlos, Rodovia Washington Luís, km 235, 13565-905, São Carlos, SP, Brazil., Cass QB; Departamento de Química, Universidade Federal de São Carlos, Rodovia Washington Luís, km 235, 13565-905, São Carlos, SP, Brazil. Electronic address: qcass@ufscar.br.
Jazyk: angličtina
Zdroj: Journal of pharmaceutical and biomedical analysis [J Pharm Biomed Anal] 2021 Jan 30; Vol. 193, pp. 113710. Date of Electronic Publication: 2020 Oct 20.
DOI: 10.1016/j.jpba.2020.113710
Abstrakt: In T. cruzi, a causative agent of Chagas disease, phosphoenolpyruvate carboxykinase (TcPEPCK) is associated with carbohydrate catabolism. Due to its importance in the metabolism of the parasite, it has become a promising target for the development of new drugs against Chagas disease. Aiming to investigate different approaches for ligands screening, TcPEPCK was immobilized on amine-terminated magnetic beads (TcPEPCK-MB) and kinetically characterized by liquid chromatography tandem mass spectrometry activity assay with a K Mapp value of 10 ± 1 μM to oxaloacetate as substrate. Natural products library affords highly diverse molecular frameworks through their secondary metabolites, herein a ligand fishing TcPEPCK-MB assay is described for prospecting ligands in four ethanolic extracts of Brazilian Cerrado plants: Qualea grandiflora (Vochysiaceae), Diospyros burchellii (Ebenaceae), Anadenanthera falcata (Fabaceae) and Byrsonima coccolobifolia (Malpighiaceae). The chemical characterization of eleven identified ligands was carried out by liquid chromatography tandem high-resolution mass spectrometry experiments. Senecic acid, syneilesinolide A, phytosphingosine and vanillic acid 4-glucopyranoside are herein reported for the first time for Q. grandiflora, D. burchellii, A. falcata, respectively. In addition, the specificity of the assay was observed since only catechin was fished out from the ethanolic extract of B. coccolobifolia leaves, despite the presence of epicatechin epimer.
Competing Interests: Declaration of Competing Interest The authors herein declare that the research was developed without private financial support or commercial relationships that could be seen as a potential conflict of interest.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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