Nitazoxanide Analogs: Synthesis, In Vitro Giardicidal Activity, and Effects on Giardia lamblia Metabolic Gene Expression
Por:
Morales-Luna L., Hernández-Ochoa B., González-Valdez A., Vázquez-Bautista M., Arreguin-Espinosa R., Pérez de la Cruz V., Enríquez-Flores S., De la Mora De la Mora I., Hernández-Urzúa E., Castillo-Rodríguez R.A., Cárdenas-Rodríguez N., Martínez-Rosas V., Navarrete-Vázquez G., Gómez-Manzo S.
Publicada:
1 ene 2025
Resumen:
Giardiasis is a common intestinal infection caused by Giardia lamblia. The standard treatment for this parasitic infection involves the administration of nitroimidazoles, albendazoles, and nitrothiazoles. However, in recent years, Giardia lamblia strains resistant to these treatments have been reported. Additionally, the current therapies exhibit considerable side effects, highlighting the need for new compounds that specifically target this parasite. The aim of this study was to evaluate nitrothiazole analogs and assess their impact on the metabolic, redox, and structural gene expression of this parasite. First, the compounds CNZ-7, CNZ-8, FLP-2, FLP-6, and FLP-8 were tested at concentrations ranging from 0 to 50 µM to determine their IC50 in G. lamblia cultures. Subsequently, gene expression changes and structural cell damage in trophozoites were analyzed following incubation with the IC50 of each compound. The giardicidal activity of the compounds was also evaluated in a nitazoxanide-resistant strain. The results showed that FLP-2, FLP-6, and FLP-8 exhibited a stronger effect on trophozoite viability compared to nitazoxanide (NTZ) and metronidazole (MTZ). Both compounds induced an increase in the expression of phosphofructokinase (PFK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase (PK), pyruvate phosphate dikinase (PPDK), and pyruvate:ferredoxin oxidoreductase (PFOR). Additionally, FLP-2 caused ultrastructural alterations in trophozoites. Furthermore, FLP-2, FLP-6, and FLP-8 demonstrated efficacy against drug-resistant strains. These findings suggest that FLP-2, FLP-6, and FLP-8 are promising candidates for the treatment of giardiasis, as they effectively reduce parasite viability, modify gene expression, and exhibit activity against drug-resistant G. lamblia strains. © 2025 by the authors.
Filiaciones:
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
Hernández-Ochoa B.:
Laboratorio de Inmunoquímica, Hospital Infantil de México Federico Gómez, Secretaría de Salud, Mexico City, 06720, Mexico
González-Valdez A.:
Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, 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
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
Enríquez-Flores S.:
Laboratorio de Biomoléculas y Salud Infantil, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City, 04530, Mexico
De la Mora De la Mora I.:
Laboratorio de Biomoléculas y Salud Infantil, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City, 04530, Mexico
Hernández-Urzúa E.:
Laboratorio de Toxicología Genética, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City, 04530, Mexico
Castillo-Rodríguez R.A.:
Centro de Investigación en Ciencia Aplicada y Tecnología Avanzada (CICATA) Unidad Morelos, Instituto Politécnico Nacional, Boulevard de la Tecnología, 1036 Z-1, P 2/2, Atlacholoaya, 62790, Mexico
Cárdenas-Rodríguez N.:
Laboratorio de Neurociencias, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City, 04530, Mexico
Martínez-Rosas V.:
Departamento de Ingeniería Química y Bioquímica, Instituto Tecnológico de, Tecnológico Nacional de México, Milpa Alta, 12300, Mexico
Navarrete-Vázquez G.:
Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Cuernavaca, Chamilpa, 62209, Mexico
Gómez-Manzo S.:
Laboratorio de Bioquímica Genética, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City, 04530, Mexico
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