4- and 5-aroylindoles as novel classes of potent antitubulin agents.
A novel series of 4- and 5-aroylindole derivatives was prepared and evaluated for antitumor activity. Several compounds showed excellent antiproliferative activity as inhibitors of tubulin polymerization. Compounds 13, 14, 15, and 18, with IC50 values of 1.9, 1.1, 1.2, and 1.8 microM, respectively, exhibited more potent inhibition of tubulin polymerization than colchicine. They also displayed antiproliferative activity, with IC50 values ranging from 10 to 43 nM in a variety of human cell lines from different organs.
Liou
Jing-Ping
JP
College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan, Republic of China.
Wu
Chang-Ying
CY
Hsieh
Hsing-Pang
HP
Chang
Chi-Yen
CY
Chen
Chi-Ming
CM
Kuo
Ching-Chuan
CC
Chang
Jang-Yang
JY
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D001704:Biopolymers; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003078:Colchicine / Q000737:chemistry; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000970:Antineoplastic Agents; D001704:Biopolymers; D007211:Indoles; D050257:Tubulin Modulators; D003078:Colchicine