Laboratorio de Inmunoquímica, Hospital Infantil de México Federico Gómez, Secretaría de Salud, Ciudad de Mexico 06720, Mexico.
Laboratorio de Bioquímica Genética, Instituto Nacional de Pediatría, Secretaría de Salud, Ciudad de México 04530, Mexico.
Molecules. 2020 Sep 1;25(17):3979. doi: 10.3390/molecules25173979.
Giardiasis is a diarrheal disease that is highly prevalent in developing countries. Several drugs are available for the treatment of this parasitosis; however, failures in drug therapy are common, and have adverse effects and increased resistance of the parasite to the drug, generating the need to find new alternative treatments. In this study, we synthesized a series of 2-mercaptobenzimidazoles that are derivatives of omeprazole, and the chemical structures were confirmed through mass, H NMR, and C NMR techniques. The in vitro efficacy compounds against , as well as its effect on the inhibition of triosephosphate isomerase (TPI) recombinant, were investigated, the inactivation assays were performed with 0.2 mg/mL of the enzyme incubating for 2 h at 37 °C in TE buffer, pH 7.4 with increasing concentrations of the compounds. Among the target compounds, , , and had greater antigiardial activity (IC: 36, 14, and 17 µM on trophozoites), and inhibited the TPI enzyme (: 2.3, 3.2, and 2.8 M s) respectively, loading alterations on the secondary structure, global stability, and tertiary structure of the TPI protein. Finally, we demonstrated that it had low toxicity on Caco-2 and HT29 cells. This finding makes it an attractive potential starting point for new antigiardial drugs.
贾第虫病是一种腹泻病，在发展中国家极为普遍。有几种药物可用于治疗这种寄生虫病；然而，药物治疗失败很常见，并且会产生药物副作用和寄生虫对药物的耐药性增加，这就需要寻找新的替代治疗方法。在这项研究中，我们合成了一系列 2-巯基苯并咪唑类化合物，它们是奥美拉唑的衍生物，并通过质谱、H NMR 和 C NMR 技术确认了它们的化学结构。我们研究了这些化合物对 的体外疗效，以及它们对三磷酸甘油醛异构酶（TPI）重组的抑制作用，用 0.2 mg/mL 的酶在 37°C 下于 TE 缓冲液（pH 7.4）中孵育 2 小时，用不同浓度的化合物进行失活实验。在目标化合物中，化合物 、 和 对滋养体具有更强的抗贾第虫活性（IC：36、14 和 17 µM），并分别抑制 TPI 酶（：2.3、3.2 和 2.8 M s），导致 TPI 蛋白的二级结构、整体稳定性和三级结构发生改变。最后，我们证明它对 Caco-2 和 HT29 细胞的毒性较低。这一发现使其成为新的抗贾第虫药物的有吸引力的潜在起点。
