Characterisation of the in vitro activity of a Nitazoxanide-N-methyl-1H-benzimidazole hybrid molecule against albendazole and nitazoxanide susceptible and resistant strains of Giardia intestinalis and its in vivo giardicidal activity
Título del documento: Characterisation of the in vitro activity of a Nitazoxanide-N-methyl-1H-benzimidazole hybrid molecule against albendazole and nitazoxanide susceptible and resistant strains of Giardia intestinalis and its in vivo giardicidal activity
Revue: Memorias do Instituto Oswaldo Cruz
Base de datos: PERIÓDICA
Número de sistema: 000437143
ISSN: 0074-0276
Autores: 1
2
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1
2
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Instituciones: 1Universidad Nacional Autónoma de México, Facultad de Química, Ciudad de México. México
2Instituto Politécnico Nacional, Escuela Nacional de Ciencias Biológicas, Ciudad de México. México
3Instituto Politécnico Nacional, Centro de Investigación y de Estudios Avanzados, Ciudad de México. México
4Instituto Mexicano del Seguro Social, Centro Médico Nacional Siglo XXI, Ciudad de México. México
Año:
Volumen: 115
País: Brasil
Idioma: Inglés
Tipo de documento: Artículo
Enfoque: Experimental, aplicado
Resumen en inglés It was previously demonstrated that CMC-20, a nitazoxanide and N-methyl-1H-benzimidazole hybrid molecule, had higher in vitro activity against Giardia intestinalis WB strain than metronidazole and albendazole and similar to nitazoxanide. OBJETIVES To evaluate the in vitro activity of CMC-20 against G. intestinalis strains with different susceptibility/resistance to albendazole and nitazoxanide and evaluate its effect on the distribution of parasite cytoskeletal proteins and its in vivo giardicidal activity. METHODS CMC-20 activity was tested against two isolates from patients with chronic and acute giardiasis, an experimentally induced albendazole resistant strain and a nitazoxanide resistant clinical isolate. CMC-20 effect on the distribution of parasite cytoskeletal proteins was analysed by indirect immunofluorescence and its activity was evaluated in a murine model of giardiasis. FINDINGS CMC-20 showed broad activity against susceptible and resistant strains to albendazole and nitaxozanide. It affected the parasite microtubule reservoir and triggered the parasite encystation. In this process, alpha-7.2 giardin co-localised with CWP-1 protein. CMC-20 reduced the infection time and cyst load in feces of G. muris infected mice similar to albendazole. MAIN CONCLUSIONS The in vitro and in vivo giardicidal activity of CMC-20 suggests its potential use in the treatment of giardiasis
Disciplinas: Medicina
Palabras clave: Farmacología,
Antiparasitarios,
Moleculas hibridas,
Nitazoxanida,
Benzimidazol,
Cepas resistentes,
Giardia intestinalis
Keyword: Pharmacology,
Antiparasitic agents,
Nitazoxanide,
Benzimidazole,
Hybrid molecules,
Resistant strains,
Giardia intestinalis
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