Morales-Luna Laura, Hernández-Ochoa Beatriz, González-Valdez Abigail, Vázquez-Bautista Montserrat, Arreguin-Espinosa Roberto, Pérez de la Cruz Verónica, Enríquez-Flores Sergio, De la Mora De la Mora Ignacio, Hernández-Urzúa Elizabeth, Castillo-Rodríguez Rosa Angélica, Cárdenas-Rodríguez Noemí, Martínez-Rosas Víctor, Navarrete-Vázquez Gabriel, Gómez-Manzo Saúl
Laboratorio de Bioquímica Genética, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City 04530, Mexico.
Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico.
Int J Mol Sci. 2025 May 8;26(10):4504. doi: 10.3390/ijms26104504.
Giardiasis is a common intestinal infection caused by . The standard treatment for this parasitic infection involves the administration of nitroimidazoles, albendazoles, and nitrothiazoles. However, in recent years, strains resistant to these treatments have been reported. Additionally, the current therapies exhibit considerable side effects, highlighting the need for new compounds that specifically target this parasite. The aim of this study was to evaluate nitrothiazole analogs and assess their impact on the metabolic, redox, and structural gene expression of this parasite. First, the compounds CNZ-7, CNZ-8, FLP-2, FLP-6, and FLP-8 were tested at concentrations ranging from 0 to 50 µM to determine their IC in cultures. Subsequently, gene expression changes and structural cell damage in trophozoites were analyzed following incubation with the IC of each compound. The giardicidal activity of the compounds was also evaluated in a nitazoxanide-resistant strain. The results showed that FLP-2, FLP-6, and FLP-8 exhibited a stronger effect on trophozoite viability compared to nitazoxanide (NTZ) and metronidazole (MTZ). Both compounds induced an increase in the expression of phosphofructokinase (, glyceraldehyde-3-phosphate dehydrogenase , pyruvate kinase , pyruvate phosphate dikinase , and pyruvate:ferredoxin oxidoreductase (. Additionally, FLP-2 caused ultrastructural alterations in trophozoites. Furthermore, FLP-2, FLP-6, and FLP-8 demonstrated efficacy against drug-resistant strains. These findings suggest that FLP-2, FLP-6, and FLP-8 are promising candidates for the treatment of giardiasis, as they effectively reduce parasite viability, modify gene expression, and exhibit activity against drug-resistant strains.
贾第虫病是一种由……引起的常见肠道感染。这种寄生虫感染的标准治疗方法包括使用硝基咪唑类、阿苯达唑和硝基噻唑类药物。然而，近年来，已报道了对这些治疗产生耐药性的菌株。此外，目前的疗法有相当多的副作用，这凸显了需要有专门针对这种寄生虫的新化合物。本研究的目的是评估硝基噻唑类似物，并评估它们对这种寄生虫的代谢、氧化还原和结构基因表达的影响。首先，测试了化合物CNZ - 7、CNZ - 8、FLP - 2、FLP - 6和FLP - 8在0至50 μM浓度范围内对培养物中其半数抑制浓度（IC）的影响。随后，在用每种化合物的IC孵育后，分析滋养体中的基因表达变化和细胞结构损伤。还在耐硝唑尼特的菌株中评估了这些化合物的杀贾第虫活性。结果表明，与硝唑尼特（NTZ）和甲硝唑（MTZ）相比，FLP - 2、FLP - 6和FLP - 8对滋养体活力的影响更强。这两种化合物均诱导磷酸果糖激酶（……）、甘油醛 - 3 - 磷酸脱氢酶（……）、丙酮酸激酶（……）、丙酮酸磷酸双激酶（……）和丙酮酸：铁氧还蛋白氧化还原酶（……）的表达增加。此外，FLP - 2导致滋养体超微结构改变。此外，FLP - 2、FLP - 6和FLP - 8对耐药菌株显示出疗效。这些发现表明，FLP - 2、FLP - 6和FLP - 8有望成为治疗贾第虫病的候选药物，因为它们能有效降低寄生虫活力、改变基因表达并对耐药菌株表现出活性。
