Cyclopamine analogs bearing exocyclic methylenes are highly potent and acid-stable inhibitors of hedgehog signaling

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-r...

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Detalles Bibliográficos
Autores principales: Moschner, Johann, Chentsova, Anna, Eilert, Nicole, Rovardi, Irene, Heretsch, Philipp, Giannis, Athanassios
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Beilstein-Institut 2013
Materias:
Full Research Paper
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3869244/
https://www.ncbi.nlm.nih.gov/pubmed/24367396
http://dx.doi.org/10.3762/bjoc.9.267
Descripción
Sumario: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.

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