Psammaplin A as a general activator of cell-based signaling assays via HDAC inhibition and studies on some bromotyrosine derivatives
| Autor: | Chris M. Ireland, Tim S. Bugni, Nikhil Banerjee, Kendell M. Cannon, Malcolm W.B. McCulloch, David M. Virshup, Mary Kay Harper, Gary S. Coombs, Charles A. Veltri |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Magnetic Resonance Spectroscopy
Clinical Biochemistry Pharmaceutical Science Biochemistry Article Cell Line Drug Discovery Animals Disulfides Enzyme Inhibitors Molecular Biology chemistry.chemical_classification Activator (genetics) Cell growth Drug discovery Organic Chemistry Wnt signaling pathway Biological activity Porifera Histone Deacetylase Inhibitors Enzyme chemistry Tyrosine Molecular Medicine Histone deacetylase Signal transduction Signal Transduction |
| Zdroj: | Bioorganic & Medicinal Chemistry. 17:2189-2198 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2008.10.077 |
| Popis: | The Wnt signaling pathway regulates cell growth and development in metazoans, and is therefore of interest for drug discovery. By screening a library of 5,808 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect