Design and Synthesis of New Withaferin A Inspired Hedgehog Pathway Inhibitors.
2-piperidine ethanol
Hedgehog inhibitors
Hedgehog signalling pathway
natural products
withaferin A
Journal
Chemistry (Weinheim an der Bergstrasse, Germany)
ISSN: 1521-3765
Titre abrégé: Chemistry
Pays: Germany
ID NLM: 9513783
Informations de publication
Date de publication:
04 Jun 2021
04 Jun 2021
Historique:
received:
26
02
2021
pubmed:
4
4
2021
medline:
10
6
2021
entrez:
3
4
2021
Statut:
ppublish
Résumé
Withanolides constitute a well-known family of plant-based alkaloids characterised by widespread biological properties, including the ability of interfering with Hedgehog (Hh) signalling pathway. Following our interest in natural products and in anticancer compounds, we report here the synthesis of a new class of Hh signalling pathway inhibitors, inspired by withaferin A, the first isolated member of withanolides. The decoration of our scaffolds was rationally supported by in silico studies, while functional evaluation revealed promising candidates, confirming once again the importance of natural products as inspiration source for the discovery of novel bioactive compounds. A stereoselective approach, based on Brown chemistry, allowed the obtainment and the functional evaluation of the enantiopure hit compounds.
Identifiants
pubmed: 33811701
doi: 10.1002/chem.202100315
pmc: PMC8251939
doi:
Substances chimiques
Antineoplastic Agents
0
Hedgehog Proteins
0
Withanolides
0
withaferin A
L6DO3QW4K5
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
8350-8357Subventions
Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca
ID : Project 20175XBSX4_003
Informations de copyright
© 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.
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