title: Synthesis and structure-activity relationships of 1-benzyl-4,5,6-trimethoxyindoles as a novel class of potent antimitotic agents.
abstract: 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).
authors.affiliation: Taipei Medical University, Taiwan, Republic of China.
authors.forename: Mei-Jung
authors.initials: MJ
authors.lastname: Lai
authors.forename: Ching-Chuan
authors.initials: CC
authors.lastname: Kuo
authors.forename: Teng-Kuang
authors.initials: TK
authors.lastname: Yeh
authors.forename: Hsing-Pang
authors.initials: HP
authors.lastname: Hsieh
authors.forename: Li-Tzong
authors.initials: LT
authors.lastname: Chen
authors.forename: Wen-Yu
authors.initials: WY
authors.lastname: Pan
authors.forename: Kuang-Yang
authors.initials: KY
authors.lastname: Hsu
authors.forename: Jang-Yang
authors.initials: JY
authors.lastname: Chang
authors.forename: Jing-Ping
authors.initials: JP
authors.lastname: Liou
mesh_terms: 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
chemical_list: D050256:Antimitotic Agents; D001688:Biological Products; D007211:Indoles; D014404:Tubulin; D001554:Benzene