Departamento de Química Orgánica and UMYMFOR (CONICET-FCEyN), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, Ciudad Universitaria, C1428EHA Buenos Aires, Argentina.
Departamento de Química Orgánica and UMYMFOR (CONICET-FCEyN), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, Ciudad Universitaria, C1428EHA Buenos Aires, Argentina.
Bioorg Med Chem. 2019 Apr 1;27(7):1350-1361. doi: 10.1016/j.bmc.2019.02.039. Epub 2019 Feb 19.
As a continuation of our project aimed at searching for new chemotherapeutic agents against American trypanosomiasis (Chagas disease), new selenocyanate derivatives were designed, synthesized and biologically evaluated against the clinically more relevant dividing form of Trypanosoma cruzi, the etiologic agent of this illness. In addition, in order to establish the role of each part of the selenocyanate moiety, different derivatives, in which the selenium atom or the cyano group were absent, were conceived, synthesized and biologically evaluated. In addition, in order to study the optimal position of the terminal phenoxy group, new regioisomers of WC-9 were synthesized and evaluated against T. cruzi. Finally, the resolution of a racemic mixture of a very potent conformationally rigid analogue of WC-9 was accomplished and further tested as growth inhibitors of T. cruzi proliferation. The results provide further insight into the role of the selenocyanate group in its antiparasitic activity.
作为我们旨在寻找新的抗美洲锥虫病（恰加斯病）化疗药物项目的延续，我们设计、合成了新的硒氰酸酯衍生物，并针对这种疾病的病原体 Trypanosoma cruzi 的更具临床相关性的分裂形式进行了生物学评估。此外，为了确定硒氰酸酯部分的每个部分的作用，我们构思、合成并对不同的衍生物进行了生物学评估，其中硒原子或氰基基团不存在。此外，为了研究末端苯氧基基团的最佳位置，我们合成了 WC-9 的新区域异构体并对其进行了针对 T. cruzi 的评估。最后，完成了一种非常强效的构象刚性 WC-9 类似物的外消旋混合物的拆分，并进一步作为 T. cruzi 增殖的生长抑制剂进行了测试。这些结果为硒氰酸酯基团在其抗寄生虫活性中的作用提供了进一步的了解。
