Chávez-Riveros Alejandra, Garrido Mariana, Ramírez Apan María Teresa, Zambrano Armando, Díaz Mario, Bratoeff Eugene
Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, D.F. 04510, Mexico.
Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, D.F. 04510, Mexico.
Eur J Med Chem. 2014 Jul 23;82:498-505. doi: 10.1016/j.ejmech.2014.06.008. Epub 2014 Jun 6.
In this study we report the cytotoxic effect on human cancer cells of two series of novel progesterone derivatives; the first containing an aromatic ester (8a-e) or a carbamate functions both linked to C-3 (9a-e) on the pregn-4,16-diene-6,20-dione skeleton. In the second series, both functional groups (ester and carbamate) are bound to C-17 on the pregn-4,6-diene-3,20-dione scaffold (13a-e and 14a-e). The panel cancer cell lines used in this study were the following: PC-3 (human prostate cancer cell line), MCF-7 (human breast cancer cell line), HCT-15 (human colon cancer cell line) and J774 (noncancerous murine macrophages) for comparison. The results from this study showed that steroid 14a, having a carbamate function at C-17, was the most potent against PC-3 cell line (96.6%) while 8c and 8e showed much higher cytotoxic activity (100%) for MCF-7 cell line. Finally, compounds 8c and 14a displayed selective properties towards tumor cell lines than noncancerous murine macrophages.
在本研究中，我们报告了两个系列新型孕酮衍生物对人癌细胞的细胞毒性作用；第一个系列含有与孕甾-4,16-二烯-6,20-二酮骨架上的C-3相连的芳香酯（8a-e）或氨基甲酸酯官能团（9a-e）。在第二个系列中，两个官能团（酯和氨基甲酸酯）都连接到孕甾-4,6-二烯-3,20-二酮支架上的C-17（13a-e和14a-e）。本研究中使用的癌细胞系如下：PC-3（人前列腺癌细胞系）、MCF-7（人乳腺癌细胞系）、HCT-15（人结肠癌细胞系）和J774（非癌性小鼠巨噬细胞）用于比较。本研究结果表明，在C-17处具有氨基甲酸酯官能团的甾体14a对PC-3细胞系的活性最强（96.6%），而8c和8e对MCF-7细胞系显示出更高的细胞毒性活性（100%）。最后，化合物8c和14a对肿瘤细胞系表现出比对非癌性小鼠巨噬细胞更具选择性的特性。
