Discovery of a new non-substrate inhibitor of the 26.5 kDa glutathione transferase from Taenia solium by virtual screening.

Autor: García-Gutiérrez P; Departamento de Química. Universidad Autónoma Metropolitana-Iztapalapa, Ciudad de México, C.P 09340, Mexico. Electronic address: pgarcia@xanum.uam.mx., Zubillaga RA; Departamento de Química. Universidad Autónoma Metropolitana-Iztapalapa, Ciudad de México, C.P 09340, Mexico., Téllez-Plancarte A; Departamento de Química. Universidad Autónoma Metropolitana-Iztapalapa, Ciudad de México, C.P 09340, Mexico., Flores-López R; Departamento de Microbiología y Parasitología, Facultad de Medicina. Universidad Nacional Autónoma de México, Ciudad de México, C.P 04510, Mexico., Camarillo-Cadena M; Departamento de Química. Universidad Autónoma Metropolitana-Iztapalapa, Ciudad de México, C.P 09340, Mexico., Landa A; Departamento de Microbiología y Parasitología, Facultad de Medicina. Universidad Nacional Autónoma de México, Ciudad de México, C.P 04510, Mexico. Electronic address: landap@unam.mx.
Jazyk: angličtina
Zdroj: Journal of molecular graphics & modelling [J Mol Graph Model] 2020 Nov; Vol. 100, pp. 107707. Date of Electronic Publication: 2020 Aug 05.
DOI: 10.1016/j.jmgm.2020.107707
Abstrakt: The inappropriate use of anthelmintics, such as praziquantel and albendazole, has generated resistance and the need to develop new drugs. Glutathione transferases, GSTs, are bisubstrate dimeric enzymes that constitute the main detoxification mechanism against electrophiles, drugs and oxidative damage in Taenia solium. Therefore, GSTs are important targets for the development of new anthelmintics. In this work, we reported a successful virtual screen aimed at the identification of novel inhibitors of a 26.5 kDa GST from T. solium (TsGST26). We found that a compound, i7, able to inhibit selectively TsGST26 concerning human GSTs, showing a non-competitive inhibition mechanism towards substrate glutathione with a K i (GSH) of 55.7 μM and mixed inhibition towards the electrophilic substrate 1-chloro-2,4-dinitrobenzene with a K i (CDNB) of 8.64 μM. These results are in agreement with those of docking simulations, which showed i7 binds a site adjacent to the electrophilic site and furthest from the glutathione site.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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