Discovery of 4-amino and 4-hydroxy-1-aroylindoles as potent tubulin polymerization inhibitors.
1-Aroylindoline, 1-aroyl-1,2,3,4-tetrahydroquinoline, and 1-aroylindole derivatives were synthesized and evaluated for anticancer activity. The 4-amino and 4-hydroxy-1-aroylindoles 26 and 27 with IC 50 of 0.9 and 0.6 microM, respectively, exhibited antitubulin activity superior or comparable to that of colchicine and combretastatin A-4. They also showed antiproliferative activity with IC 50 of 0.3-5.4 nM in a set of human cancer cell lines.
Liou
Jing-Ping
JP
College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan, Republic of China.
Wu
Zi-Yi
ZY
Kuo
Ching-Chuan
CC
Chang
Chi-Yen
CY
Lu
Pei-Yi
PY
Chen
Chi-Ming
CM
Hsieh
Hsing-Pang
HP
Chang
Jang-Yang
JY
D001704:Biopolymers / Q000737:chemistry*; D045744:Cell Line, Tumor; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization; D014404:Tubulin / Q000737:chemistry / Q000187:drug effects*
D001704:Biopolymers; D007211:Indoles; D014404:Tubulin