title: Antitumor agents. Part 186: Synthesis and biological evaluation of demethylcolchiceinamide analogues as cytotoxic DNA topoisomerase II inhibitors.
abstract: Demethylation of colchiceinamide (2) and its analogues (3-10) afforded a novel class of mammalian DNA topoisomerase II inhibitors (2a-10a) without displaying tubulin inhibitory activity. All target compounds inhibited the catalytic activity of topoisomerase II at drug concentrations at 100 microM. An in vitro cytotoxicity assay indicated that compounds 3a and 8a were strong and tissue-selective cytotoxic agents against the MCF-7 breast cancer cell line (IC50 = 0.36 and 0.48 microgram/mL, respectively) and the CAKI-1 renal cancer cell line (IC50 = 0.72 and 0.96 microgram/mL, respectively).
authors.affiliation: Natural Products Laboratory, School of Pharmacy, University of North Carolina at Chapel Hill 27599, USA.
authors.forename: J
authors.initials: J
authors.lastname: Guan
authors.forename: X K
authors.initials: XK
authors.lastname: Zhu
authors.forename: Y
authors.initials: Y
authors.lastname: Tachibana
authors.forename: K F
authors.initials: KF
authors.lastname: Bastow
authors.forename: A
authors.initials: A
authors.lastname: Brossi
authors.forename: E
authors.initials: E
authors.lastname: Hamel
authors.forename: K H
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D001943:Breast Neoplasms; D002470:Cell Survival / Q000187:drug effects; D003078:Colchicine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D005260:Female; D006801:Humans; D007202:Indicators and Reagents; D007680:Kidney Neoplasms; D007700:Kinetics; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D059005:Topoisomerase II Inhibitors; C012852:colchiceine; D003078:Colchicine