Chemistry Laboratory, Agricultural University of Athens, Iera Odos 75, Athens 11855, Greece.
Bioorg Med Chem. 2013 Jul 15;21(14):4120-31. doi: 10.1016/j.bmc.2013.05.012. Epub 2013 May 15.
A collection of compounds, structurally related to the anticancer drug tamoxifen, used in breast cancer therapy, were designed and synthesized as potential anticancer agents. McMurry coupling reaction was used as the key synthetic step in the preparation of these analogues and the structural assignment of E, Z isomers was determined on the basis of 2D-NOESY experiments. The compounds were evaluated for their antiproliferative activity on breast cancer (MCF-7), cervix adenocarcinoma (HeLa) and biphasic mesothelioma (MSTO-211H) human tumor cell lines. The estrogen like properties of the novel compounds were compared with those of the untreated controls using an estrogen responsive element-based (ERE) luciferase reporter assay and compared to 17β-estradiol (E2). Finally, with the aim to correlate the antiproliferative activity with an intracellular target(s), the effect on relaxation activity of DNA topoisomerases I and II was assayed.
设计并合成了一组与乳腺癌治疗药物他莫昔芬结构相关的化合物，作为潜在的抗癌药物。麦默瑞偶联反应被用作这些类似物制备的关键合成步骤，根据二维 NOESY 实验确定 E、Z 异构体的结构分配。评估了这些化合物对乳腺癌（MCF-7）、宫颈腺癌（HeLa）和双相间皮瘤（MSTO-211H）人肿瘤细胞系的增殖活性。使用基于雌激素反应元件（ERE）的荧光素酶报告基因测定法，将新化合物的雌激素样特性与未经处理的对照进行比较，并与 17β-雌二醇（E2）进行比较。最后，为了将增殖活性与细胞内靶标（s）相关联，测定了对 DNA 拓扑异构酶 I 和 II 松弛活性的影响。
