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

Steven Rossington; J. Hadfield; Steven D. Shnyder; Timothy Wallace; Kaye Williams

doi:10.1016/j.bmc.2017.01.027

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

Steven Rossington, J. Hadfield, Steven D. Shnyder, Timothy Wallace, Kaye Williams

Pharmacy

Research output: Contribution to journal › Article › peer-review

142 Downloads (Pure)

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.

Original language	English
Pages (from-to)	1630-1642
Number of pages	13
Journal	Bioorganic and Medicinal Chemistry
Volume	25
Issue number	5
Early online date	19 Jan 2017
DOIs	https://doi.org/10.1016/j.bmc.2017.01.027
Publication status	Published - 1 Mar 2017

Keywords

Journal Article
tubulin
Tumour vasculature
direct arylation
palladium catalyst
Colchicine

Access to Document

10.1016/j.bmc.2017.01.027

1-s2 0-S0968089616313141-mainAccepted author manuscript, 1.09 MB

1 Article

Tubulin-binding dibenz[c,e]oxepines as colchinol analogues for targeting tumour vasculature
Edwards, D. J., Hadfield, J. A., Wallace, T. W. & Ducki, S., 1 Jan 2011, In: Organic and Biomolecular Chemistry. 9, 1, p. 219-231 12 p.
Research output: Contribution to journal › Article › peer-review

Open Access
File
123 Downloads (Pure)

Cite this

@article{10b26caed0964cc39f8262516c4c4b47,

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

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.",

keywords = "Journal Article, tubulin, Tumour vasculature, direct arylation, palladium catalyst, Colchicine",

author = "Steven Rossington and J. Hadfield and Shnyder, {Steven D.} and Timothy Wallace and Kaye Williams",

year = "2017",

month = mar,

day = "1",

doi = "10.1016/j.bmc.2017.01.027",

language = "English",

volume = "25",

pages = "1630--1642",

journal = "Bioorganic and Medicinal Chemistry",

issn = "0968-0896",

publisher = "Elsevier BV",

number = "5",

}

TY - JOUR

T1 - Tubulin-binding dibenz[c,e]oxepines

T2 - Part 2. Structural variation and biological evaluation as tumour vasculature disrupting agents

AU - Rossington, Steven

AU - Hadfield, J.

AU - Shnyder, Steven D.

AU - Wallace, Timothy

AU - Williams, Kaye

PY - 2017/3/1

Y1 - 2017/3/1

N2 - 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.

AB - 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.

KW - Journal Article

KW - tubulin

KW - Tumour vasculature

KW - direct arylation

KW - palladium catalyst

KW - Colchicine

U2 - 10.1016/j.bmc.2017.01.027

DO - 10.1016/j.bmc.2017.01.027

M3 - Article

C2 - 28143677

SN - 0968-0896

VL - 25

SP - 1630

EP - 1642

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 5

ER -

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

Abstract

Keywords

Access to Document

Fingerprint

Research output

Tubulin-binding dibenz[c,e]oxepines as colchinol analogues for targeting tumour vasculature

Cite this