title: Tubulin-binding dibenz[c,e]oxepines as colchinol analogues for targeting tumour vasculature.
abstract: Various methoxy- and hydroxy-substituted dibenz[c,e]oxepines were prepared via the copper(I)-induced coupling of ether-tethered arylstannanes or the dehydrative cyclisation of 1,1'-biphenyl-2,2'-dimethanols, assembled using the Ullmann cross-coupling of ortho-bromoaryl carbonyl compounds. The dibenzoxepines were screened for their ability to inhibit tubulin polymerisation and the in vitro growth of K562 human chronic myelogenous leukemia cells. The most active was 5,7-dihydro-3,9,10,11-tetramethoxydibenz[c,e]oxepin-4-ol, whose tubulin inhibitory and cytotoxicity (IC(50)) values were 1 μM and 40 nM, respectively.
authors.affiliation: School of Chemistry, The University of Manchester, Oxford Road, Manchester, UK M13 9PL.
authors.forename: David J
authors.initials: DJ
authors.lastname: Edwards
authors.forename: John A
authors.initials: JA
authors.lastname: Hadfield
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Wallace
authors.forename: Sylvie
authors.initials: S
authors.lastname: Ducki
mesh_terms: D003990:Dibenzoxepins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D020014:K562 Cells; D008958:Models, Molecular; D009389:Neovascularization, Pathologic; D011485:Protein Binding; D014404:Tubulin / Q000737:chemistry* / Q000378:metabolism
chemical_list: C556228:5,7-dihydro-3,9,10,11-tetramethoxydibenz(c,e)oxepin-4-ol; D003990:Dibenzoxepins; D014404:Tubulin