title: Synthesis and biological evaluation of 1-(4'-Indolyl and 6'-Quinolinyl) indoles as a new class of potent anticancer agents.
abstract: A novel series of the biheterocycles-based compounds with core structure distinguished from combretastatin A-4 (1) and colchicine (5) have been synthesized and evaluated as potent anti-mitotic agents. Compound 1-(4'-Indolyl and 6'-quinolinyl)-4,5,6-trimethoxyindoles 13 and 19 showed substantial anti-proliferative activity against various human cancer cell lines, regardless to the tissue origin and the expression of multiple-drug resistance MDR1, with a mean IC(50) value of 38 and 24 nM respectively. Compound 13 (IC(50) = 1.7 μM) also exhibited similar anti-tubulin activities to 1 (IC(50) = 1.8 μM) and displayed strong binding property to the colchicine binding site on the microtubules. Computational modeling analysis revealed that the binding mechanism of compound 13 is similar to that of CA4.
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, No 250, Wuxing Street, Taipei 11031, Taiwan, ROC.
authors.forename: Mei-Jung
authors.initials: MJ
authors.lastname: Lai
authors.forename: Jang-Yang
authors.initials: JY
authors.lastname: Chang
authors.forename: Hsueh-Yun
authors.initials: HY
authors.lastname: Lee
authors.forename: Ching-Chuan
authors.initials: CC
authors.lastname: Kuo
authors.forename: Mei-Hsiang
authors.initials: MH
authors.lastname: Lin
authors.forename: Hsing-Pang
authors.initials: HP
authors.lastname: Hsieh
authors.forename: Chi-Yen
authors.initials: CY
authors.lastname: Chang
authors.forename: Jian-Sung
authors.initials: JS
authors.lastname: Wu
authors.forename: Su-Ying
authors.initials: SY
authors.lastname: Wu
authors.forename: Kuang-Shing
authors.initials: KS
authors.lastname: Shey
authors.forename: Jing-Ping
authors.initials: JP
authors.lastname: Liou
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D021241:Spectrometry, Mass, Electrospray Ionization; D014404:Tubulin / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D014404:Tubulin