Proteomic and ultrastructural analysis of the effect of a new nitazoxanide-N-methyl-1H-benzimidazole hybrid against Giardia intestinalis

Matadamas-Martínez, Félix; Castillo, Rafael; Hernández‐Campos, Alicia; Méndez-Cuesta, Carlos A.; Souza, Wanderley de; Gadelha, Ana Paula Rocha; Nogueda‐Torres, Benjamín; Hernández, José Manuel; Yépez‐Mulia, Lilián

doi:10.1016/j.rvsc.2016.02.006

Cited by 15 publications

(23 citation statements)

References 34 publications

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“…Chemistry -The benzimidazole derivative CMC-20 was prepared as previously described by our group. (16) The chemical formula of CMC-20 is presented as Supplementary data.…”

Section: Methodsmentioning

confidence: 99%

“…Cytotoxicity assay -Madin-Darby canine kidney cell line (MDCK) was used to assess the cytotoxic effect of ABZ and NTZ as previously described for CMC-20. (16) The cells were cultured in standard culture medium [MEM with 10% foetal bovine serum (FBS)]. The final concentration of DMSO in the culture medium remained below 0.01%.…”

Section: Methodsmentioning

confidence: 99%

“…IFI assays -For this purpose, trophozoites of G. intestinalis WB strain (2 X 10 6 ) were incubated for 24 h in culture medium with CMC-20 at the same concen-tration (7.8 µM) previously used for proteomic studies. (16) Trophozoites without treatment were included as negative control. Control and CMC-20 treated parasites were placed on poly-L-lysine coated glass slides (Sigma-Aldrich) and incubated for 10 min to allow cells to attach to the glass surface.…”

Section: Methodsmentioning

confidence: 99%

“…Cytotoxicity assays -The cytotoxicity of CMC-20, ABZ and NTZ was tested on Madin-Darby canine kidney cell line (MDCK) and their CC 50 values were > 26 µM, (16) > 37.6 µM and > 32.5 µM, respectively. To calculate their selectivity index (SI) against the parasite strains, CC 50 values of 26 µM, 37.6 µM and 32.5 µM of CMC-20, ABZ and NTZ, respectively, were used (Table).…”

Section: Activity Of Cmc-20 Against G Intestinalis Strains -mentioning

confidence: 99%

“…The proteomic analysis of CMC-20 treated trophozoites revealed significant changes in the expression level of alpha and beta tubulin, as well as some proteins that participate in the encystment process. (16) Since CMC-20 showed potent activity against WB strain, a reference strain susceptible to ABZ and NTZ, our interest was to evaluate its giardicidal activity against parasite strains susceptible or resistant to these reference drugs. These strains included an isolate from a patient with chronic giardiasis and one from a patient with acute giardiasis; an experimentally induced ABZ resistant strain and a NTZ resistant clinical isolate.…”

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confidence: 99%

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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

Matadamas-Martínez

Nogueda‐Torres

Castillo

et al. 2020

Mem. Inst. Oswaldo Cruz

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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.

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“…Chemistry -The benzimidazole derivative CMC-20 was prepared as previously described by our group. (16) The chemical formula of CMC-20 is presented as Supplementary data.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Activity Of Cmc-20 Against G Intestinalis Strains -mentioning

confidence: 99%

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confidence: 99%

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