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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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 - Does NOT include content added after October 2018:	Biomedical Research Centre
Identification Number:	https://doi.org/10.1016/j.bmc.2008.10.077
Page Range:	2189-2198
Depositing User:	Users 3084 not found.
Date Deposited:	10 May 2013 09:06
Last Modified:	18 Mar 2021 23:45
URI:	https://shura.shu.ac.uk/id/eprint/7010

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