Synthesis and biological evaluation of novel 2-(2-arylmethylene)hydrazinyl-4-aminoquinazoline derivatives as potent antitumor agents.
Two series of novel 2-(2-arylmethylene)hydrazinyl-4-aminoquinazoline derivatives were synthesized and evaluated for their cytotoxicity against H-460, HT-29, HepG2 and SGC-7901 cancer cell lines in vitro. Most compounds displayed moderate to excellent activity, with IC(50) values ranging from 0.015 to 4.09 μM against all tested cell lines, respectively. The most promising compound 9p (E)-2-(2-((1-(2,3-dichlorobenzyl)-1H-imidazol-2-yl)methylene)hydrazinyl)-N-(1-methylpiperidin-4-yl)quinazolin-4-amine with IC(50) values of 0.031 μM, 0.015 μM, 0.53 μM and 0.58 μM, which was 4- to 224 times more active than references 10 and Iressa, had emerged as a lead for further structural modifications.
Key Lab of New Drugs Design and Discovery of Liaoning Province, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 110016 Shenyang, PR China.
Nan
N
Jiang
Xin
X
Zhai
Yanfang
Y
Zhao
Yajing
Y
Liu
Baohui
B
Qi
Haiyan
H
Tao
Ping
P
Gong
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D006801:Humans; D020128:Inhibitory Concentration 50; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D011799:Quinazolines