Novel angular furoquinolinones bearing flexible chain as antitumor agent: design, synthesis, cytotoxic evaluation, and DNA-binding studies.
A series of novel N-substituted angular furoquinolinone derivatives were synthesized and evaluated for their antitumor activities against QGY, K562, HeLa, P388, and A549 cell lines in vitro. The derivatives bearing basic amino side chain showed an improved antitumor activity. Compound 5h N-(2-dimethylamino-ethyl)-2-(4,8,9-trimethyl-2-oxo-2H-furo[2,3-h]quinolin-1-yl)-acetamide exhibited the highest activities against P388 and A549 cell lines, which are evidenced by the IC(50) values that are four to five fold lower than that for unsubstituted parent compound. DNA-binding experiments suggested that these derivatives bind to DNA through intercalation.
Xie
Lijuan
L
State Key Laboratory of Fine Chemicals, Dalian University of Technology, PO Box 89, Zhongshan Road 158, Dalian 116012, China.
Qian
Xuhong
X
Cui
Jingnan
J
Xiao
Yi
Y
Wang
Kewei
K
Wu
Peichun
P
Cong
Liying
L
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D015195:Drug Design; D005663:Furans / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D015363:Quinolones / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D005663:Furans; D015363:Quinolones; D004247:DNA