Structural requirements for the interaction of combretastatins with tubulin: how important is the trimethoxy unit?

You do not have JavaScript enabled. Please enable JavaScript to access the full features of the site or access our non-JavaScript page.

Structural requirements for the interaction of combretastatins with tubulin: how important is the trimethoxy unit?†

Keira Gaukroger,^a John A Hadfield,*^ab Nicholas J Lawrence,^cd Steven Nolan^a and Alan T McGown^ab

Author affiliations

* Corresponding authors

^a Drug Development Section, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester

^b Centre for Molecular Drug Design, Cockcroft Building, University of Salford, Manchester

^c Department of Chemistry, UMIST, PO Box 88, Manchester

^d Department of Chemistry, Cardiff University, PO Box 912, Cardiff

Abstract

A series of combretastatins possessing both a trimethoxy unit and other substituents on ring A has been synthesised and tested for cytotoxicity and their ability to interact with the protein tubulin. All previous studies have indicated that the trimethoxy unit is essential for interaction with tubulin. The studies herein show that molecules possessing functionalities other than trimethoxy can also interact with tubulin. Importantly a trimethyl substituted agent 52a has shown reduced cytotoxicity, but increased potency in its ability to inhibit the assembly of tubulin.

Download options Please wait...

Supplementary files

Experimental details DOC (140K)

Article information

DOI: https://doi.org/10.1039/B306878A
Article type: Paper
Submitted: 19 Jun 2003
Accepted: 09 Jul 2003
First published: 24 Jul 2003

Download Citation

Org. Biomol. Chem., 2003,1, 3033-3037

Permissions

Request permissions