title: Antitumor Agents. 211. Fluorinated 2-phenyl-4-quinolone derivatives as antimitotic antitumor agents.
abstract: Fluorinated 2-phenyl-4-quinolone derivatives were synthesized and evaluated in National Cancer Institute's 60 human tumor cell line in vitro screen. From the results, the ketone moiety plays an essential role in activity. Among the compounds tested, 2'-fluoro-6-pyrrol-2-phenyl-4-quinolone (13) exhibited the most potent cytotoxic activities (log GI(50) < -8.00) against renal and melanoma tumor cell lines. Compound 13 was also a potent inhibitor of tubulin polymerization (IC(50) = 0.46 microM) and of radiolabeled colchicine binding to tubulin, with activities comparable to those of the potent antimitotic natural products colchicine, podophyllotoxin, and combretastatin A-4.
authors.affiliation: Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599-7360, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Xia
authors.forename: Z Y
authors.initials: ZY
authors.lastname: Yang
authors.forename: P
authors.initials: P
authors.lastname: Xia
authors.forename: T
authors.initials: T
authors.lastname: Hackl
authors.forename: E
authors.initials: E
authors.lastname: Hamel
authors.forename: A
authors.initials: A
authors.lastname: Mauger
authors.forename: J H
authors.initials: JH
authors.lastname: Wu
authors.forename: K H
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001704:Biopolymers; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008938:Mitosis / Q000187:drug effects; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry; D014407:Tumor Cells, Cultured
chemical_list: C439962:2'-fluoro-6-pyrrol-2-phenyl-4-quinolone; D000970:Antineoplastic Agents; D001704:Biopolymers; D011758:Pyrroles; D015363:Quinolones; D014404:Tubulin