Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia; Department of Chemistry, Faculty of Science, Alexandria University, P.O. Box 426, Alexandria 21321, Egypt.
Bioproducts Research Chair, College of Science, Department of Zoology, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
Bioorg Chem. 2020 Jan;94:103397. doi: 10.1016/j.bioorg.2019.103397. Epub 2019 Oct 29.
Here we report on a small library based on a 4-aminobenzonitile-s-triazine moiety. We used a straightforward orthogonal synthetic pathway to prepare di- and tri-substituted s-triazine derivatives, whose basic structure was modified. The newly synthesized compounds were fully characterized by H NMR, C NMR and elemental analysis. They showed strong anticancer activity against two human breast cancer cell lines (MIDA-MB-231 and MCF-7), with IC values less than 1 µM. These s-triazine compounds were generally more selective towards hormone receptor-positive breast cancer cell line MCF-7 than the triple negative MDA-MB-231 cell line. Zebrafish embryos were used to test the developmental toxicity of the target compounds in vivo. The phenotype of embryos treated with the derivatives resembled that of those treated with estrogen disruptors. This observation strongly supports the notion that that these compounds induce their anticancer activity in human breast cancer cells via targeting the estrogen and progesterone receptors.
我们在此报告了一个基于 4-氨基苯甲腈-s-三嗪部分的小型化合物库。我们使用直接的正交合成途径来制备二取代和三取代的 s-三嗪衍生物，其基本结构进行了修饰。新合成的化合物通过 1 H NMR、13 C NMR 和元素分析进行了充分表征。它们对两种人乳腺癌细胞系（MIDA-MB-231 和 MCF-7）表现出强烈的抗癌活性，IC 值小于 1µM。这些 s-三嗪化合物对激素受体阳性乳腺癌细胞系 MCF-7 的选择性通常高于三阴性 MDA-MB-231 细胞系。斑马鱼胚胎被用于体内测试目标化合物的发育毒性。用衍生物处理的胚胎的表型类似于用雌激素破坏剂处理的胚胎。这一观察结果强烈支持这样一种观点，即这些化合物通过靶向雌激素和孕激素受体，在人乳腺癌细胞中诱导其抗癌活性。
