Synthesis and structure-activity relationships of 1-benzyl-4,5,6-trimethoxyindoles as a novel class of potent antimitotic agents.
A series of 1-benzyl-4,5,6-trimethoxyindoles was designed and prepared as a novel class of potent antimitotic agents acting through the colchicine binding site of tubulin. Compounds 10 and 11 showed excellent antiproliferative activity with mean IC(50) values of 26 and 27 nM, respectively, in a diverse set of human cancer lines from different organs, including a MDR+ line. They also displayed substantial antitubulin efficacy with IC(50) values of 3.5 and 2.6 muM, respectively, representing an improvement over colchicine (IC(50)=4.3 muM).
Lai
Mei-Jung
MJ
Taipei Medical University, Taiwan, Republic of China.
Kuo
Ching-Chuan
CC
Yeh
Teng-Kuang
TK
Hsieh
Hsing-Pang
HP
Chen
Li-Tzong
LT
Pan
Wen-Yu
WY
Hsu
Kuang-Yang
KY
Chang
Jang-Yang
JY
Liou
Jing-Ping
JP
D050256:Antimitotic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001554:Benzene / Q000737:chemistry*; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008938:Mitosis / Q000187:drug effects; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000378:metabolism
D050256:Antimitotic Agents; D001688:Biological Products; D007211:Indoles; D014404:Tubulin; D001554:Benzene