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Tubulin-binding dibenz[c,e]oxepines. Part 2. 1 Structural variation and biological evaluation as tumour vasculature disrupting agents
Rossington, S.B. Hadfield, J.A. Wallace, T.W. Williams, K.J.
Rossington, S.B.
Hadfield, J.A.
Wallace, T.W.
Williams, K.J.
Publication Date
2017-03-01
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© 2017 Elsevier. Reproduced in accordance with the publisher's selfarchiving
policy. This manuscript version is made available under the CC-BY-NC-ND 4.0
license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Peer-Reviewed
Yes
Open Access status
openAccess
Accepted for publication
2017-01-17
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Abstract
5,7-Dihydro-3,9,10,11-tetramethoxybenz[c,e]oxepin-4-ol 1, prepared from a dibenzyl ether
precursor via Pd-catalysed intramolecular direct arylation, possesses broad-spectrum in
vitro cytotoxicity towards various tumour cell lines, and induces vascular shutdown,
necrosis and growth delay in tumour xenografts in mice at sub-toxic doses. The biological
properties of 1 and related compounds can be attributed to their ability to inhibit
microtubule assembly at the micromolar level, by binding reversibly to the same site of the
tubulin αβ-heterodimer as colchicine 2 and the allocolchinol, N-acetylcolchinol 4.
Version
Accepted manuscript
Citation
Rossington SB, Hadfield JA, Shnyder SA et al (2017) Tubulin-binding
dibenz[c,e]oxepines: Part 2. 1 Structural variation and biological evaluation as tumour vasculature disrupting agents. Bioorganic and Medicinal Chemistry. 25(5): 1630-1642.
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Article