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Novel cyanocombretastatins as potent tubulin polymerisation inhibitors

Jalily, Pouria; Hirst, N; Hadfield, JA; Rossington, SB

Authors

Pouria Jalily

N Hirst

JA Hadfield

SB Rossington



Abstract

A series of novel cyanocombretastatins bearing a 3,4,5-trimethoxyphenyl moiety combined with a variety of substituted phenyl rings, were synthesised and their antitumour activity was evaluated. The Z-cyanocombretastatins were synthesised in a one-step protocol in high purity and yield. Fluoro, bromo,
iodo, and derivatives with boronic acid and an ethyne function at meta position of the B ring were synthesised. In vitro MTT bioassays against human chronic myelogenous leukaemia (K562) and transfected breast adenocarcinoma (MDA NQO1) cell lines, revealed promising IC50 inhibitory values in nanomolar
range (<50 nM). Introduction of a nitrile function on the olefinic bond not only increased the cytotoxicity of the less active Z-isomers but rendered the analogues as moderate to potent inhibitors of tubulin polymerisation comparable to that of CA-4 (IC50 = 2.2 lM).

Citation

Jalily, P., Hirst, N., Hadfield, J., & Rossington, S. (2012). Novel cyanocombretastatins as potent tubulin polymerisation inhibitors. Bioorganic and Medicinal Chemistry Letters, 22(21), 6731-6734. https://doi.org/10.1016/j.bmcl.2012.08.089

Journal Article Type Article
Acceptance Date Aug 23, 2012
Online Publication Date Sep 6, 2012
Publication Date Sep 6, 2012
Deposit Date Oct 8, 2012
Journal Bioorganic and medicinal chemistry letters
Print ISSN 0960-894X
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 22
Issue 21
Pages 6731-6734
DOI https://doi.org/10.1016/j.bmcl.2012.08.089
Publisher URL http://dx.doi.org/10.1016/j.bmcl.2012.08.089
Related Public URLs http://www.sciencedirect.com/science/journal/0960894X/22/21