Cyclopamine analogs bearing exocyclic methylenes are highly potent and acid-stable inhibitors of hedgehog signaling
| Autor: | Philipp Heretsch, Irene Rovardi, Anna Chentsova, Athanassios Giannis, Johann Moschner, Nicole Eilert |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
steroidal alkaloids
structure–activity relationship Cyclopamine Stereochemistry natural products Organic Chemistry Chemical synthesis Combinatorial chemistry Hedgehog signaling pathway Full Research Paper lcsh:QD241-441 chemistry.chemical_compound Chemistry chemistry Nitrogen atom lcsh:Organic chemistry Acid stable Structure–activity relationship Luciferase lcsh:Q cyclopamine hedgehog signaling pathway lcsh:Science Methyl group |
| Zdroj: | Beilstein Journal of Organic Chemistry, Vol 9, Iss 1, Pp 2328-2335 (2013) Beilstein Journal of Organic Chemistry |
| ISSN: | 1860-5397 |
| Popis: | The chemical synthesis and biological evaluation of new cyclopamine analogs bearing exocyclic methylenes in different positions is described. Bis-exo-cyclopamine 6 was identified as a potent inhibitor of the Gli1-dependent luciferase expression in Shh-LIGHTII cells. An extension of this study to F-ring-modified structures shows the necessity of a rigidly positioned nitrogen atom for bioactivity as well as the presence of the C21 methyl group for acid stability and bioactivity. |
| Databáze: | OpenAIRE |
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