Universidad de Talca, Casilla 747, Talca, Chile.
Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad de Concepción, Casilla 160-C, Concepción, Chile.
Bioorg Chem. 2020 Oct;103:104122. doi: 10.1016/j.bioorg.2020.104122. Epub 2020 Jul 23.
A new library of twenty triazole-lapachol and nor-lapachol derivatives was synthesized. The compounds were evaluated against the epimastigotes form of Trypanosoma cruzi and promastigotes of Leishmania braziliensis and L. infantum. The cytotoxicity of the compounds was determined on murine fibroblasts and used to assess the selectivity index. The introduction of triazole rings in the naphthoquinone derivatives improved activity against the parasitic protozoa T. cruzi and Leishmania species. Some of the derivatives were three to six times more potent than benznidazole against T. cruzi, with similar or slightly better selectivity indexes. The results against L. braziliensis showed that the derivatives 5b and 5e were the most selective compounds. However, they were less selective than the reference compound, miltefosine. Among all products, the derivative 3a was the most selective compound against L. infantum. Nevertheless, it was less potent and less selective than miltefosine. Also, the minimum inhibitory concentration values of the derivatives against nine different bacteria were determined. Moderate antibacterial activity was observed for compound 5c against Staphylococcus aureus.
合成了 20 种三唑-拉帕醌和去甲拉帕醌衍生物的新库。对这些化合物进行了评价，以评估它们对克氏锥虫的滋养体形式和巴西利什曼原虫和婴儿利什曼原虫的前体的活性。通过测定化合物对鼠成纤维细胞的细胞毒性，并用其来评估选择性指数。在萘醌衍生物中引入三唑环可以提高对寄生原生动物克氏锥虫和利什曼原虫属的活性。一些衍生物对克氏锥虫的活性比苯并硝唑高 3 至 6 倍，且具有相似或稍高的选择性指数。对巴西利什曼原虫的研究结果表明，衍生物 5b 和 5e 是最具选择性的化合物。然而，它们的选择性不如参考化合物米替福新。在所有产品中，衍生物 3a 对婴儿利什曼原虫的选择性最高。然而，它的活性和选择性都不如米替福新。此外，还测定了这些衍生物对 9 种不同细菌的最小抑菌浓度值。化合物 5c 对金黄色葡萄球菌具有中等的抗菌活性。
