UMYMFOR-CONICET - Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pab 2 1428, Buenos Aires, Argentina.
Bioorg Med Chem Lett. 2013 Sep 1;23(17):4964-7. doi: 10.1016/j.bmcl.2013.06.064. Epub 2013 Jul 3.
Secochiliolide acid (1) isolated from the Patagonian shrub Nardophyllum bryoides, was used as a scaffold for the preparation of a series of nine derivatives. Compound 1 and its derivatives were tested against Trypanosoma cruzi epimastigotes grown in liquid media. It was first observed that secochiliolide acid (1) inhibited the proliferation of the parasites, with an IC50 of 2 μg/mL. Six of the synthesized derivatives were also active with IC50's between 2 and 7 μg/mL which are comparable to that of the commercial drug benznidazole (2.5 μg/mL). These results indicate that the carboxyl group is not essential for the bioactivity of 1, while the presence of the tetrasubstituted exocyclic double bond seems to be important. Moreover, the presence of the furan and spirolactone rings is not essential for the bioactivity per se, but is important in combination with other structural fragments present in the molecule.
从巴塔哥尼亚灌木纳多菲勒中分离出的 secochiliolide 酸（1）被用作制备一系列九个衍生物的支架。将化合物 1 及其衍生物用于测试在液体培养基中生长的克氏锥虫滋养体。首先观察到 secochiliolide 酸（1）抑制寄生虫的增殖，IC50 为 2μg/mL。合成的 6 种衍生物也具有活性，IC50 在 2 到 7μg/mL 之间，与商业药物苯并咪唑（2.5μg/mL）相当。这些结果表明，羧基对于 1 的生物活性不是必需的，而四取代的环外双键的存在似乎很重要。此外，呋喃和螺内酯环的存在对于生物活性本身不是必需的，但与分子中存在的其他结构片段结合很重要。
