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

Félix Matadamas-Martínez, Benjamín Nogueda-Torres, Rafael Castillo, Alicia Hernández-Campos, María de la Luz Barrera-Valdes, Gloria León-ávila, José Manuel Hernández, Lilián Yépez-Mulia

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    Abstract

    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.

    Original languageEnglish
    Article numbere190348
    JournalMemorias do Instituto Oswaldo Cruz
    Volume115
    DOIs
    StatePublished - 1 Jan 2020

    Keywords

    • Cytoskeletal proteins
    • Giardicidal activity
    • Hybrid molecule
    • In vivo activity
    • Resistant strains

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