| Autor: |
Martínez-Rosas V; Laboratorio de Bioquímica Genética, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City 04530, Mexico.; Programa de Posgrado en Biomedicina y Biotecnología Molecular, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City 11340, Mexico., Navarrete-Vázquez G; Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Chamilpa, Cuernavaca 62209, Mexico., Ortega-Cuellar D; Laboratorio de Nutrición Experimental, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City 04530, Mexico., Arreguin-Espinosa R; Departamento de Química de Biomacromoléculas, Instituto de Química, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico., Pérez de la Cruz V; Neurobiochemistry and Behavior Laboratory, National Institute of Neurology and Neurosurgery 'Manuel Velasco Suárez', Mexico City 14269, Mexico., Calderón-Jaimes E; Laboratorio de Inmunoquímica, Hospital Infantil de México Federico Gómez, Secretaría de Salud, Mexico City 06720, Mexico., Enríquez-Flores S; Laboratorio de Biomoléculas y Salud Infantil, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City 04530, Mexico., Wong-Baeza C; Laboratorio de Biomembranas, Departamento de Bioquímica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City 11350, Mexico., Baeza-Ramírez I; Laboratorio de Biomembranas, Departamento de Bioquímica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City 11350, Mexico., Morales-Luna L; Laboratorio de Bioquímica Genética, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City 04530, Mexico.; Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico., Vázquez-Bautista M; Laboratorio de Bioquímica Genética, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City 04530, Mexico.; Programa de Posgrado en Biomedicina y Biotecnología Molecular, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City 11340, Mexico., Rojas-Alarcón MA; Laboratorio de Bioquímica Genética, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City 04530, Mexico.; Programa de Posgrado en Biomedicina y Biotecnología Molecular, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City 11340, Mexico., Hernández-Ochoa B; Laboratorio de Inmunoquímica, Hospital Infantil de México Federico Gómez, Secretaría de Salud, Mexico City 06720, Mexico., Gómez-Manzo S; Laboratorio de Bioquímica Genética, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City 04530, Mexico. |
| Abstrakt: |
Metronidazole (MTZ) is the most common drug used against Trichomonas vaginalis ( T. vaginalis ) infections; however, treatment failures and high rates of recurrence of trichomoniasis have been reported, suggesting the presence of resistance in T. vaginalis to MTZ. Therefore, research into new therapeutic options against T. vaginalis infections has become increasingly urgent. This study investigated the trichomonacidal activity of a series of five imidazole carbamate compounds (AGR-1, AGR-2, AGR-3, AGR-4, and AGR-5) through in vitro susceptibility assays to determine the IC 50 value of each compound. All five compounds demonstrated potent trichomonacidal activity, with IC 50 values in the nanomolar range and AGR-2 being the most potent (IC 50 400 nM). To gain insight into molecular events related to AGR-induced cell death in T. vaginalis , we analyzed the expression profiles of some metabolic genes in the trophozoites exposed to AGR compounds and MTZ. It was found that both AGR and MTZ compounds reduced the expression of the glycolytic genes ( CK , PFK , TPI , and ENOL ) and genes involved in metabolism ( G6PD , TKT , TALDO , NADHOX , ACT , and TUB ), suggesting that disturbing these key metabolic genes alters the survival of the T. vaginalis parasite and that they probably share a similar mechanism of action. Additionally, the compounds showed low cytotoxicity in the Caco-2 and HT29 cell lines, and the results of the ADMET analysis indicated that these compounds have pharmacokinetic properties similar to those of MTZ. The findings offer significant insights that can serve as a basis for future in vivo studies of the compounds as a potential new treatment against T. vaginalis . |
