Universidad Nacional Autónoma de México, Facultad de Química, Departamento de Farmacia, Mexico City, Mexico.
Instituto Mexicano del Seguro Social, Centro Médico Siglo XXI, Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, Hospital de Pediatría, Mexico City, Mexico.
Mem Inst Oswaldo Cruz. 2020 Feb 7;115:e190348. doi: 10.1590/0074-02760190348. eCollection 2020.
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.
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.
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.
The in vitro and in vivo giardicidal activity of CMC-20 suggests its potential use in the treatment of giardiasis.
先前的研究表明，硝唑尼特和 N-甲基-1H-苯并咪唑杂合分子 CMC-20 对肠贾第虫 WB 株的体外活性高于甲硝唑和阿苯达唑，与硝唑尼特相似。
评估 CMC-20 对阿苯达唑和硝唑尼特敏感性/耐药性不同的肠贾第虫株的体外活性，并评估其对寄生虫细胞骨架蛋白分布的影响及其体内杀贾第虫活性。
对两名慢性和急性贾第虫病患者的分离株、经实验诱导的阿苯达唑耐药株和临床耐药的硝唑尼特分离株进行 CMC-20 活性测试。通过间接免疫荧光分析 CMC-20 对寄生虫细胞骨架蛋白分布的影响，并在鼠贾第虫病模型中评估其活性。
CMC-20 对阿苯达唑和硝唑尼特敏感和耐药株均具有广泛的活性。它影响寄生虫微管库并触发寄生虫包囊形成。在此过程中，α-7.2 贾第虫与 CWP-1 蛋白共定位。CMC-20 减少了感染时间和粪便中 G. muris 感染小鼠的囊泡负荷，与阿苯达唑相似。
CMC-20 的体外和体内杀贾第虫活性表明其在贾第虫病治疗中的潜在用途。
