Department of Pharmaceutical Chemistry, College of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
Molecules. 2021 Feb 22;26(4):1170. doi: 10.3390/molecules26041170.
Several derivatives containing morpholine/piperidine, anilines, and dipeptides as pending moieties were prepared using -triazine as a scaffold. These compounds were evaluated for their anticancer activity against two human breast cancer cell lines (MCF-7 and MDA-MB-231), a colon cancer cell line (HCT-116), and a non-tumorigenic cell line (HEK 293). Tamoxifen was used as a reference. Animal toxicity tests were carried out in zebrafish embryos. Most of these compounds showed a higher activity against breast cancer than colon cancer. Compound -which contains morpholine, aniline, and glycylglycinate methyl ester-showed a high level of cytotoxicity against MCF-7 cells with IC values of less than 1 µM. This compound showed a much lower level of toxicity against the non-tumorigenic HEK-293 cell line, and in the in vivo studies using zebrafish embryos. Furthermore, it induced cell cycle arrest at the G2/M phase, and apoptosis in MCF-7 cells. On the basis of our results, emerges as a potential candidate for further development as a therapeutic drug to treat hormone receptor-positive breast cancer.
使用 -三嗪作为支架，制备了几种包含吗啉/哌啶、苯胺和二肽作为悬垂部分的衍生物。这些化合物针对两种人乳腺癌细胞系（MCF-7 和 MDA-MB-231）、一种结肠癌细胞系（HCT-116）和一种非致瘤细胞系（HEK 293）进行了抗癌活性评估。他莫昔芬被用作参考。在斑马鱼胚胎中进行了动物毒性测试。这些化合物中的大多数对乳腺癌的活性都高于结肠癌。含有吗啉、苯胺和甘氨酰甘氨酸甲酯的化合物 -对 MCF-7 细胞表现出高细胞毒性，IC 值低于 1 µM。与非致瘤性的 HEK-293 细胞系相比，该化合物的毒性要低得多，在使用斑马鱼胚胎的体内研究中也是如此。此外，它诱导 MCF-7 细胞的细胞周期停滞在 G2/M 期，并诱导细胞凋亡。根据我们的结果， -作为一种有潜力的候选药物，可进一步开发用于治疗激素受体阳性乳腺癌。
