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.
College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan, Republic of China.
Jing-Ping
JP
Liou
Chang-Ying
CY
Wu
Hsing-Pang
HP
Hsieh
Chi-Yen
CY
Chang
Chi-Ming
CM
Chen
Ching-Chuan
CC
Kuo
Jang-Yang
JY
Chang
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