Psammaplin A as a general activator of cell-based signaling assays via HDAC inhibition and studies on some bromotyrosine derivatives

MCCULLOCH, Malcolm W.B., COOMBS, Gary S., BANERJEE, Nikhil, BUGNI, Tim S., CANNON, Kendell M., HARPER, Mary Kay, VELTRI, Charles A., VIRSHUP, David M. and IRELAND, Chris M. (2009). Psammaplin A as a general activator of cell-based signaling assays via HDAC inhibition and studies on some bromotyrosine derivatives. Bioorganic and Medicinal Chemistry, 17 (6), 2189-2198.

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Official URL: http://dx.doi.org/10.1016/j.bmc.2008.10.077
Link to published version:: 10.1016/j.bmc.2008.10.077

Abstract

The Wnt signaling pathway regulates cell growth and development in metazoans, and is therefore of interest for drug discovery. By screening a library of 5808 pre-fractionated marine extracts in a cell-based Wnt signaling assay, several signaling activators and inhibitors were observed. LCMS-based fractionation rapidly identified an active compound from Pseudoceratina purpurea as psammaplin A, a known HDAC inhibitor. Other HDAC inhibitors similarly activated signaling in this assay, indicating HDAC inhibitors will be identified through many cell-based reporter assays. In a large scale analysis of P. purpurea, three previously undescribed bromotyrosine based natural products were identified; the structure of one of these was confirmed by synthesis. Additionally, three other derivatives of psammaplin A were prepared: a mixed disulfide and two sulfinate esters. Finally, evidence to support a structural reassignment of psammaplin I from a sulfone to the isomeric sulfinate ester is presented.

Item Type: Article
Research Institute, Centre or Group: Biomolecular Sciences Research Centre
Identification Number: 10.1016/j.bmc.2008.10.077
Depositing User: Marguerite Lyons
Date Deposited: 10 May 2013 09:06
Last Modified: 10 May 2013 09:06
URI: http://shura.shu.ac.uk/id/eprint/7010

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