Key Laboratory of Original New Drug Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang, Liaoning 110016, PR China.
Eur J Med Chem. 2010 Aug;45(8):3504-10. doi: 10.1016/j.ejmech.2010.05.016. Epub 2010 May 12.
In an attempt to develop potent and selective antitumor agents, a series of novel 1,4-disubstituted phthalazine derivatives was designed and synthesized. All the prepared compounds were screened for their cytotoxic activities against A549, HT-29 and MDA-MB-231 cell lines in vitro. Among them, seven compounds (7a-7e, 7j and 7i) displayed excellent selectivity for MDA-MB-231 cells with IC(50) values in the nM range, a desirable range for pharmacological testing. The most promising compound, 7a (IC(50) = 3.79 microM, 2.32 microM, 0.84 nM), was 5.6-, 10.8- and 6.9 x 10(4)- times more active than PTK-787 (IC(50) = 21.16 microM, 22.11 microM, 57.72 microM), respectively.
为了开发有效且选择性高的抗肿瘤药物，设计并合成了一系列新型的 1,4-取代的酞嗪衍生物。所有合成的化合物均进行了体外细胞毒性实验，以评估其对 A549、HT-29 和 MDA-MB-231 细胞株的抑制活性。其中，7 个化合物（7a-7e、7j 和 7i）对 MDA-MB-231 细胞具有优异的选择性，IC50 值在纳摩尔范围内，这是药理学测试的理想范围。最有前途的化合物 7a（IC50 = 3.79μM、2.32μM、0.84nM）对 PTK-787（IC50 = 21.16μM、22.11μM、57.72μM）的活性分别提高了 5.6 倍、10.8 倍和 6.9 倍。
