Antitrichomonal activity and docking analysis of thiazole derivatives as TvMP50 protease inhibitors
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PROTOZOOLOGY - ORIGINAL PAPER
Antitrichomonal activity and docking analysis of thiazole derivatives as TvMP50 protease inhibitors Gonzalo Mena-Rejón 1 & Yussel Pérez-Navarro 2 & Julio César Torres-Romero 1 & Laura Vázquez-Carrillo 2 & Rubén M. Carballo 1 & Rodrigo Arreola 3 & Ángel Herrera-España 1 & Victor Arana-Argáez 1 & Ramiro Quijano-Quiñones 1 & Jose Manuel Fernández-Sánchez 4 & María Elizbeth Alvarez-Sánchez 2 Received: 22 June 2020 / Accepted: 11 October 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Trichomoniasis, caused by the protozoan Trichomonas vaginalis, is the most prevalent non-viral sexually transmitted infection that affects over 170 million people worldwide. The only type of drug recommended for the therapeutic control of trichomoniasis is the 5-nitroimidazoles, although there have been reports of some undesirable side effects and clinical resistance. Hence, the need for the search for new tricomonicidal agents is necessary. In a previous work, we demonstrated that two 2-amino-4-aryl thiazole derivatives (ATZ-1 and ATZ-2) possess a portent antigiardial effect. In the current paper, we investigated the in vitro antitrichomonal activity of these thiazole compounds. Both ATZ-1 and ATZ-2 reduced the viability and growth of parasites in a dose-dependent manner, with an IC50 value of 0.15 μg/mL and 0.18 μg/mL, respectively. Furthermore, both thiazole compounds were able to decrease the proteolytic activity in T. vaginalis trophozoites compared with untreated parasites. Interestingly, a full proteolytic inhibition profile was observed in the 50-kDa region which was associated with the decreased expression of the gene that codes for the trichomonad protease TvMP50. The docking simulations predicted strong interactions of the thiazole compounds in the TvMP50 protease’s active site, suggesting a possible role as protease inhibitors. Our results demonstrate the potential of 2-amino-4-aryl thiazole derivatives as trichomonicidal compounds and could be, mechanistically, involved in the inhibition of key trichomonad proteases. Keywords Trichomoniasis . T. vaginalis . Thiazole . Anti-proteolytic . TvMP50
Introduction Section Editor: Kevin S.W. Tan * María Elizbeth Alvarez-Sánchez [email protected]; [email protected] 1
Facultad de Química, Universidad Autónoma de Yucatán (UADY), Calle 43 S/N entre calle 96 y calle 40, Colonia Inalámbrica, C.P. 97069 Mérida, Yucatán, México
2
Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México (UACM), San Lorenzo # 290, Col. Del Valle, CP 03100 México City, México
3
Psychiatric Genetics Department, Clinical Research Branch, National Institute of Psychiatry, Ramón de la Fuente, Calzada México-Xochimilco 101, Colonia San Lorenzo Huipulco, Tlalpan, 14370 México City, DF, México
4
División de Ingeniería en Gestión Empresarial, Tecnológico de Estudios Superiores de Ecatepec, Avenida Tecnológico S/N, Colonia Valle de Anahuac, Ecatepec de Morelos, Estado de México, Mexico
Sexually transmitted infections (STIs) ar
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