Novel cyanocombretastatins as potent tubulin polymerisation inhibitors

Jalily, Pouria, Hirst, N, Hadfield, JA ORCID: https://orcid.org/0000-0001-7984-8319 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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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:	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:	Publication
Depositing User:	JA Hadfield
Date Deposited:	08 Oct 2012 11:58
Last Modified:	16 Feb 2022 14:35
URI:	https://usir.salford.ac.uk/id/eprint/25244

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