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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • McCulloch, MWB; Coombs, GS; Banerjee, N; Bugni, TS; Cannon, KM; Harper, MK; Veltri, CA; Virshup, DM; Ireland, CM

Published Date

  • March 15, 2009

Published In

Volume / Issue

  • 17 / 6

Start / End Page

  • 2189 - 2198

PubMed ID

  • 19022675

Pubmed Central ID

  • PMC2670876

Electronic International Standard Serial Number (EISSN)

  • 1464-3391

Digital Object Identifier (DOI)

  • 10.1016/j.bmc.2008.10.077


  • eng

Conference Location

  • England