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 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 .