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.
Eur J Med Chem. 2013 Nov;69:480-9. doi: 10.1016/j.ejmech.2013.09.009. Epub 2013 Sep 18.
As a part of our project pointed at the search of new safe chemotherapeutic and chemoprophylactic agents against parasitic diseases, several compounds structurally related to 4-phenoxyphenoxyethyl thiocyanate (WC-9), which were modified at the terminal aromatic ring, were designed, synthesized and evaluated as antiproliferative agents against Trypanosoma cruzi, the parasite responsible of American trypanosomiasis (Chagas disease) and Toxoplasma gondii, the etiological agent of toxoplasmosis. Most of the synthetic analogs exhibited similar antiparasitic activity being slightly more potent than the reference compound WC-9. For example, the nitro derivative 13 showed an ED₅₀ value of 5.2 μM. Interestingly, the regioisomer of WC-9, compound 36 showed similar inhibitory action than WC-9 indicating that para-phenyl substitution pattern is not necessarily required for biological activity. The biological evaluation against T. gondii was also very promising. The ED₅₀ values corresponding for 13, 36 and 37 were at the very low micromolar level against tachyzoites of T. gondii.
作为我们项目的一部分，该项目旨在寻找针对寄生虫病的新型安全化疗和化学预防药物，我们设计、合成并评估了几种结构上与 4-苯氧基苯氧基乙基硫氰酸酯（WC-9）相关的化合物，这些化合物在末端芳环上进行了修饰，作为抗增殖剂对抗引起美洲锥虫病（恰加斯病）的寄生虫克氏锥虫和引起弓形体病的病原体弓形体。大多数合成类似物表现出相似的抗寄生虫活性，比参考化合物 WC-9 略强。例如，硝基衍生物 13 的 ED₅₀ 值为 5.2 μM。有趣的是，WC-9 的区域异构体化合物 36 表现出与 WC-9 相似的抑制作用，表明对苯环的取代模式不一定是生物活性所必需的。对弓形体的生物评价也非常有希望。化合物 13、36 和 37 的 ED₅₀ 值在针对弓形体速殖子的非常低的微摩尔水平。
