Lo Yu-Hsiang, Lin I-Ling, Lin Chi-Fong, Hsu Cheng-Chung, Yang Sheng-Huei, Lin Shinne-Ren, Wu Ming-Jung
Graduate Institute of Pharmaceutical Science, Kaohsiung Medical University, Kaohsiung, Taiwan.
Bioorg Med Chem. 2007 Jul 1;15(13):4528-36. doi: 10.1016/j.bmc.2007.04.024. Epub 2007 Apr 19.
A series of acyclic enediynes showing significant inhibition on the growth of tumor cancer is disclosed. To investigate the structure-activity relationship, compounds 12-33 were synthesized. Among them, compound 17 showed most potent growth inhibition activity against all tumor cell lines at low concentration, such as SR (0.4microM) and MDA-MB-435 (0.8microM), and almost completely blocked cell cycle in G2/M phase via controlling Cyclin A and Cdc25C expression. On the other hand, compound 29 showed potent induced apoptosis activity by inducing activation of caspase-3, -8, and -9. Thus, this article disclosed a new multiple-protein regulator in cell cycle regulation and induced apoptosis to achieve the goal of anticancer drug.
公开了一系列对肿瘤癌症生长具有显著抑制作用的无环烯二炔。为了研究构效关系，合成了化合物12 - 33。其中，化合物17在低浓度下对所有肿瘤细胞系表现出最有效的生长抑制活性，如SR（0.4微摩尔）和MDA - MB - 435（0.8微摩尔），并通过控制细胞周期蛋白A和Cdc25C的表达几乎完全阻断G2/M期的细胞周期。另一方面，化合物29通过诱导半胱天冬酶-3、-8和-9的激活表现出有效的诱导凋亡活性。因此，本文公开了一种新的多蛋白调节剂，用于细胞周期调节和诱导凋亡以实现抗癌药物的目标。
