Skip to the content

Novel cyanocombretastatins as potent tubulin polymerisation inhibitors

Jalily, Pouria, Hirst, N, Hadfield, JA and Rossington, SB 2012, 'Novel cyanocombretastatins as potent tubulin polymerisation inhibitors' , Bioorganic and medicinal chemistry letters . (In Press)

[img] PDF - Published Version
Restricted to Repository staff only

Download (780kB) | Request a copy

    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).

    Item Type: Article
    Themes: Health and Wellbeing
    Schools: Colleges and Schools > College of Science & Technology
    Colleges and Schools > College of Science & Technology > School of Environment and Life Sciences > Biomedical Research Centre
    Colleges and Schools > College of Science & Technology > School of Environment and Life Sciences
    Journal or Publication Title: Bioorganic and medicinal chemistry letters
    Publisher: Elsevier
    Refereed: Yes
    ISSN: 0960-894X
    Depositing User: JA Hadfield
    Date Deposited: 08 Oct 2012 12:58
    Last Modified: 10 Jul 2014 14:18
    URI: http://usir.salford.ac.uk/id/eprint/25244

    Actions (login required)

    Edit record (repository staff only)

    Downloads per month over past year

    View more statistics