Triosephosphate isomerase as a therapeutic target against trichomoniasis.

Autor: Benítez-Cardoza CG; Laboratorio de Investigación Bioquímica, ENMyH-Instituto Politécnico Nacional, Ciudad de México, Mexico., Brieba LG; Laboratorio Nacional de Genómica para la Biodiversidad Centro de Investigación y de Estudios Avanzados del IPN, Guanajuato, Mexico., Arroyo R; Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del IPN, Mexico., Rojo-Domínguez A; Departamento de Ciencias Naturales, Universidad Autónoma Metropolitana Cuajimalpa, CDMX, Mexico., Vique-Sánchez JL; Facultad de Medicina Mexicali, Universidad Autónoma de Baja California, BC, Mexico. Electronic address: jvique@uabc.edu.mx.
Jazyk: angličtina
Zdroj: Molecular and biochemical parasitology [Mol Biochem Parasitol] 2021 Nov; Vol. 246, pp. 111413. Date of Electronic Publication: 2021 Sep 16.
DOI: 10.1016/j.molbiopara.2021.111413
Abstrakt: Trichomoniasis is the most common non-viral sexually transmitted infection, caused by the protozoan parasite Trichomonas vaginalis, affecting millions of people worldwide. The main treatment against trichomoniasis is metronidazole and other nitroimidazole derivatives, but up to twenty percent of clinical cases of trichomoniasis are resistant to these drugs. In this study, we used high-performance virtual screening to search for molecules that specifically bind to the protein, triosephosphate isomerase from T. vaginalis (TvTIM). By in silico molecular docking analysis, we selected six compounds from a chemical library of almost 500,000 compounds. While none of the six inhibited the enzymatic activity of recombinant triosephosphate isomerase isoforms, one compound (A4; 3,3'-{[4-(4-morpholinyl)phenyl]methylene}bis(4- hydroxy-2H-chromen-2-one) altered their fluorescence emission spectra, suggesting that this chemical might interfere in an important non-glycolytic function of TvTIM. In vitro assays demonstrate that A4 is not cytotoxic but does have trichomonacidal impact on T. vaginalis cultures. With these results, we propose this compound as a potential drug with a new therapeutic target against Trichomonas vaginalis.
(Copyright © 2021 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: