Synthesis and cytotoxic evaluation of some new phthalazinylpiperazine derivatives

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.