| Autor: |
García-Torres I; Laboratorio de Biomoléculas y Salud Infantil, Instituto Nacional de Pediatría, CDMX, México., De la Mora-De la Mora I; Laboratorio de Biomoléculas y Salud Infantil, Instituto Nacional de Pediatría, CDMX, México., López-Velázquez G; Laboratorio de Biomoléculas y Salud Infantil, Instituto Nacional de Pediatría, CDMX, México., Cabrera N; Departamento de Bioquímica y Biología Estructural, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, CDMX, México., Flores-López LA; CONAHCYT Instituto Nacional de Pediatría, Laboratorio de Biomoléculas y Salud Infantil, CDMX, México., Becker I; Centro de Medicina Tropical, Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, CDMX, México., Herrera-López J; Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, CDMX, México., Hernández R; Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, CDMX, México., Pérez-Montfort R; Departamento de Bioquímica y Biología Estructural, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, CDMX, México., Enríquez-Flores S; Laboratorio de Biomoléculas y Salud Infantil, Instituto Nacional de Pediatría, CDMX, México. |
| Abstrakt: |
Trypanosoma cruzi is the causative agent of American trypanosomiasis, which mainly affects populations in Latin America. Benznidazole is used to control the disease, with severe effects in patients receiving this chemotherapy. Previous studies have demonstrated the inhibition of triosephosphate isomerase from T. cruzi , but cellular enzyme inhibition has yet to be established. This study demonstrates that rabeprazole inhibits both cell viability and triosephosphate isomerase activity in T. cruzi epimastigotes. Our results show that rabeprazole has an IC 50 of 0.4 µM, which is 14.5 times more effective than benznidazole. Additionally, we observed increased levels of methyl-glyoxal and advanced glycation end products after the inhibition of cellular triosephosphate isomerase by rabeprazole. Finally, we demonstrate that the inactivation mechanisms of rabeprazole on triosephosphate isomerase of T. cruzi can be achieved through the derivatization of three of its four cysteine residues. These results indicate that rabeprazole is a promising candidate against American trypanosomiasis. |
