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 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.
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.
Shulan
S
Zhang
Yanfang
Y
Zhao
Yajing
Y
Liu
Dong
D
Chen
Weihuan
W
Lan
Qiaoling
Q
Zhao
Chengcheng
C
Dong
Lin
L
Xia
Ping
P
Gong
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D010793:Phthalazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D010793:Phthalazines; C043388:phthalazine