5-Amino-2-aroylquinolines as highly potent tubulin polymerization inhibitors.
A series of aroylquinoline derivatives were synthesized and evaluated for anticancer activity. 5-Amino-6-methoxy-2-aroylquinoline 15 showed more potent antiproliferative activity (IC(50) values ranging from 0.2 to 0.4 nM) as compared to 1a (combretastatin A-4) (IC(50) = 1.9-835 nM) against various human cancer cell lines and a MDR-resistant cancer cell line. Compound 15 (IC(50) = 1.6 microM) exhibited more potent inhibition of tubulin polymerization than 1a (IC(50) = 2.1 microM) and showed strong binding property to the colchicine binding site of microtubules.
Nien
Chih-Ying
CY
College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan, Republic of China.
Chen
Yun-Ching
YC
Kuo
Ching-Chuan
CC
Hsieh
Hsing-Pang
HP
Chang
Chi-Yen
CY
Wu
Jian-Sung
JS
Wu
Su-Ying
SY
Liou
Jing-Ping
JP
Chang
Jang-Yang
JY
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000502:physiology*; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000970:Antineoplastic Agents; D011804:Quinolines; D014404:Tubulin; D050257:Tubulin Modulators