TY - JOUR
T1 - 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
AU - Matadamas-Martínez, Félix
AU - Nogueda-Torres, Benjamín
AU - Castillo, Rafael
AU - Hernández-Campos, Alicia
AU - de la Luz Barrera-Valdes, María
AU - León-ávila, Gloria
AU - Hernández, José Manuel
AU - Yépez-Mulia, Lilián
N1 - Publisher Copyright:
© 2020, Fundacao Oswaldo Cruz. All rights reserved.
PY - 2020
Y1 - 2020
N2 - BACKGROUND 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 immunof luorescence 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.
AB - BACKGROUND 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 immunof luorescence 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.
KW - Cytoskeletal proteins
KW - Giardicidal activity
KW - Hybrid molecule
KW - In vivo activity
KW - Resistant strains
UR - http://www.scopus.com/inward/record.url?scp=85079334972&partnerID=8YFLogxK
U2 - 10.1590/0074-02760190348
DO - 10.1590/0074-02760190348
M3 - Artículo
C2 - 32049098
AN - SCOPUS:85079334972
SN - 0074-0276
VL - 115
JO - Memorias do Instituto Oswaldo Cruz
JF - Memorias do Instituto Oswaldo Cruz
M1 - e190348
ER -