| Institution: | 1. Department of Chemistry, Università degli Studi di Milano, Via Golgi 19, 20133 Milan, Italy;2. Department of Biotechnology, Chemistry and Pharmacy Università degli Studi di Siena, Via Aldo Moro 2, 53100 Siena, Italy;3. Istituto Italiano di Tecnologia, Viale Regina Elena 291, 00161 Rome, Italy;4. Department of Molecular Medicine, University La Sapienza, Roma, Viale Regina Elena 291, 00161 Roma, Italy;5. Department of Molecular Medicine, University La Sapienza, Roma, Viale Regina Elena 291, 00161 Roma, Italy
Laboratory affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Molecular Medicine, University La Sapienza, Viale Regina Elena 291, 00161 Roma, Italy;6. Department of Chemistry and Technology of Drugs, University La Sapienza, Roma, Piazzale Aldo Moro 5, 00185 Rome, Italy;7. Arkansas State University, Campus Querétaro Carretera Estatal 100, km 17.5. C.P., 76270 Municipio de Colón Querétaro, México |
| 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. |
