Novel cyanocombretastatins as potent tubulin polymerisation inhibitors

Jalily, Pouria, Hirst, N, Hadfield, JA ORCID: and Rossington, SB 2012, 'Novel cyanocombretastatins as potent tubulin polymerisation inhibitors' , Bioorganic and medicinal chemistry letters, 22 (21) , pp. 6731-6734.

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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).

Item Type: Article
Themes: Health and Wellbeing
Schools: Schools > School of Environment and Life Sciences > Biomedical Research Centre
Journal or Publication Title: Bioorganic and medicinal chemistry letters
Publisher: Elsevier
Refereed: Yes
ISSN: 0960-894X
Related URLs:
Depositing User: JA Hadfield
Date Deposited: 08 Oct 2012 11:58
Last Modified: 16 Feb 2022 14:35

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