Synthesis and antitumor activities of novel 1,4-disubstituted phthalazine derivatives

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 IC50 values in the nM range, a desirable range for pharmacological testing. The most promising compound, 7a (IC50 = 3.79 μM, 2.32 μM, 0.84 nM), was 5.6-, 10.8- and 6.9 × 104- times more active than PTK-787 (IC50 = 21.16 μM, 22.11 μM, 57.72 μM), respectively.

Graphical abstractThe most promising compound, 7a (IC50 = 3.79 μM, 2.32 μM, 0.84 nM), showed excellent cytotoxic activities against A549, HT-29 and MDA-MB-231 cell lines in vitro by the MTT method.Figure optionsDownload full-size imageDownload as PowerPoint slide