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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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
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author Moschner, Johann
Chentsova, Anna
Eilert, Nicole
Rovardi, Irene
Heretsch, Philipp
Giannis, Athanassios
author_facet Moschner, Johann
Chentsova, Anna
Eilert, Nicole
Rovardi, Irene
Heretsch, Philipp
Giannis, Athanassios
author_sort Moschner, Johann
collection PubMed
description 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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spelling pubmed-38692442013-12-23 Cyclopamine analogs bearing exocyclic methylenes are highly potent and acid-stable inhibitors of hedgehog signaling Moschner, Johann Chentsova, Anna Eilert, Nicole Rovardi, Irene Heretsch, Philipp Giannis, Athanassios Beilstein J Org Chem Full Research Paper 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. Beilstein-Institut 2013-10-31 /pmc/articles/PMC3869244/ /pubmed/24367396 http://dx.doi.org/10.3762/bjoc.9.267 Text en Copyright © 2013, Moschner et al. https://creativecommons.org/licenses/by/2.0https://www.beilstein-journals.org/bjoc/termsThis is an Open Access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The license is subject to the Beilstein Journal of Organic Chemistry terms and conditions: (https://www.beilstein-journals.org/bjoc/terms)
spellingShingle Full Research Paper
Moschner, Johann
Chentsova, Anna
Eilert, Nicole
Rovardi, Irene
Heretsch, Philipp
Giannis, Athanassios
Cyclopamine analogs bearing exocyclic methylenes are highly potent and acid-stable inhibitors of hedgehog signaling
title Cyclopamine analogs bearing exocyclic methylenes are highly potent and acid-stable inhibitors of hedgehog signaling
title_full Cyclopamine analogs bearing exocyclic methylenes are highly potent and acid-stable inhibitors of hedgehog signaling
title_fullStr Cyclopamine analogs bearing exocyclic methylenes are highly potent and acid-stable inhibitors of hedgehog signaling
title_full_unstemmed Cyclopamine analogs bearing exocyclic methylenes are highly potent and acid-stable inhibitors of hedgehog signaling
title_short Cyclopamine analogs bearing exocyclic methylenes are highly potent and acid-stable inhibitors of hedgehog signaling
title_sort cyclopamine analogs bearing exocyclic methylenes are highly potent and acid-stable inhibitors of hedgehog signaling
topic Full Research Paper
url 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
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