Tubulin-binding dibenz[c,e]oxepines. Part 2. 1 Structural variation and biological evaluation as tumour vasculature disrupting agents

Description

Yes / 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.

Links & Downloads

1. 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.
2. http://hdl.handle.net/10454/11235
3. https://doi.org/10.1016/j.bmc.2017.01.027

Tags

Intramolecular direct arylation

Tubulin targeting

Tumour growth inhibition

Vascular shutdown

Colchicinoid

Dibenz[c,e]oxepine

Additional Fields

Identifer	oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/11235
Date	19 January 2017
Creators	Rossington, S.B., Hadfield, J.A., Shnyder, Steven, Wallace, T.W., Williams, K.J.
Source Sets	Bradford Scholars
Language	English
Detected Language	English
Type	Article, Accepted manuscript
Rights	© 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/), CC-BY-NC-ND