Key Laboratory of Original New Drug Design and Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, China.
Arch Pharm (Weinheim). 2012 Apr;345(4):287-93. doi: 10.1002/ardp.201100250. Epub 2011 Oct 18.
A new series of 1,4-disubstituted phthalazinylpiperazine derivatives 7a-f, 12a-f and 20a-f were designed and synthesized in order to develop potent and selective antitumor agents. The target compounds were screened for their cytotoxic activities against A549, HT-29 and MDA-MB-231 cancer cell lines in vitro. Among them, compounds 7a-f exhibited excellent selectivity for MDA-MB-231 with IC(50) values ranging from 0.013 µM to 0.079 µM. The most promising compound, 7e (IC(50) = 2.19 µM, 2.19 µM, 0.013 µM), was 9.3, 10, and 4.9 × 10(3) times more active than vatalanib (IC(50) = 20.27 µM, 21.96 µM, 63.90 µM), respectively.
为了开发有效的抗肿瘤药物，设计并合成了一系列新的 1,4-二取代邻苯二甲酰亚氨基哌嗪衍生物 7a-f、12a-f 和 20a-f。对目标化合物进行了体外细胞毒性筛选，以评估其对 A549、HT-29 和 MDA-MB-231 癌细胞系的活性。其中，化合物 7a-f 对 MDA-MB-231 具有优异的选择性，IC50 值范围为 0.013 μM 至 0.079 μM。最有前途的化合物 7e（IC50 = 2.19 μM，2.19 μM，0.013 μM）对 vatalanib（IC50 = 20.27 μM，21.96 μM，63.90 μM）的活性分别提高了 9.3、10 和 4.9 倍。
