Harrity, J.P.A., Brown, A., Holmes, T. et al. (3 more authors) (2018) Evaluation of sydnone-based analogs of combretastatin A-4 phosphate (CA4P) as vascular disrupting agents for use in cancer therapy. ChemMedChem, 13 (24). pp. 2618-2626. ISSN 1860-7179
Abstract
The combretastatins have attracted significant interest as small molecule therapies for cancer due to their ability to function as vascular disrupting agents. We have successfully prepared a range of combretastatin analogs that are based on a novel sydnone heterocycle core, and their potential as tubulin has been assessed in vitro and in vivo. The most potent candidate was found to disrupt microtubules and affect cellular morphology at sub-micromolar levels. Moreover, it was found to bind reversibly to tubulin and significantly increase endothelial cell monolayer permeability, in a similar manner to combretastatin A4. Surprisingly, the compound did not exhibit efficacy in vivo, possibly due to rapid metabolism.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. This is an author-produced version of a paper subsequently published in ChemMedChem. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Palladium Catalysis; Sydnone; Tubulin Binders; Vascular Disrupting Agents; cancer |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > Department of Chemistry (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 15 Oct 2018 10:19 |
Last Modified: | 03 May 2024 15:45 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1002/cmdc.201800567 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:137134 |