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.

Design and Synthesis of New Withaferin A Inspired Hedgehog Pathway Inhibitors / E. Bonandi, M. Mori, P. Infante, I. Basili, L. Di Marcotullio, A. Calcaterra, F. Catti, B. Botta, D. Passarella. - In: CHEMISTRY-A EUROPEAN JOURNAL. - ISSN 0947-6539. - 27:32(2021 Jun 04), pp. 8350-8357. [10.1002/chem.202100315]

Design and Synthesis of New Withaferin A Inspired Hedgehog Pathway Inhibitors

E. Bonandi
Primo
;
P. Infante;D. Passarella
Ultimo
2021-06-04

Abstract

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.
2-piperidine ethanol; Hedgehog inhibitors; Hedgehog signalling pathway; natural products; withaferin A; Hedgehog Proteins; Signal Transduction; Antineoplastic Agents; Withanolides
Settore CHIM/06 - Chimica Organica
3-apr-2021
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/890674
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