title: Synthesis and biological evaluation of colchicine B-ring analogues tethered with halogenated benzyl moieties.
abstract: Deacetylcolchicine was reacted with substituted benzyl halides to provide a library of compounds for biological analysis. Compound 7 (3,4-difluorobenzyl-N-aminocolchicine) was shown to possess cytotoxicity in cancer cell lines in the low nanomolar range. Significantly, it showed no loss of activity in the resistant A2780AD ovarian carcinoma cell line known to overexpress the ABCB1 drug transporter and was also unaffected by overexpression of class III β-tubulin in HeLa transfected cells.
authors.affiliation: Institute of Cancer Therapeutics, University of Bradford, Bradford, West Yorkshire, BD7 1DP, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Cosentino
authors.forename: Mariano
authors.initials: M
authors.lastname: Redondo-Horcajo
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
authors.forename: Ana Rita
authors.initials: AR
authors.lastname: Santos
authors.forename: Kaniz F
authors.initials: KF
authors.lastname: Chowdury
authors.forename: Victoria
authors.initials: V
authors.lastname: Vinader
authors.forename: Qasem M A
authors.initials: QM
authors.lastname: Abdallah
authors.forename: Hamdy
authors.initials: H
authors.lastname: Abdel-Rahman
authors.forename: Jérémie
authors.initials: J
authors.lastname: Fournier-Dit-Chabert
authors.forename: Steven D
authors.initials: SD
authors.lastname: Shnyder
authors.forename: Paul M
authors.initials: PM
authors.lastname: Loadman
authors.forename: Wei-shuo
authors.initials: WS
authors.lastname: Fang
authors.forename: José Fernando
authors.initials: JF
authors.lastname: Díaz
authors.forename: Isabel
authors.initials: I
authors.lastname: Barasoain
authors.forename: Philip A
authors.initials: PA
authors.lastname: Burns
authors.forename: Klaus
authors.initials: K
authors.lastname: Pors
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001665:Binding Sites; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D003078:Colchicine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008870:Microtubules / Q000187:drug effects / Q000648:ultrastructure; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D014162:Transfection; D014404:Tubulin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: C578809:(3,4-difluorobenzyl-N-aminocolchicine); D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D014404:Tubulin; D050257:Tubulin Modulators; D003078:Colchicine