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- Title
Biology-Oriented Synthesis of a Withanolide-Inspired Compound Collection Reveals Novel Modulators of Hedgehog Signaling.
- Authors
Švenda, Jakub; Sheremet, Michael; Kremer, Lea; Maier, Lukáš; Bauer, Jonathan O.; Strohmann, Carsten; Ziegler, Slava; Kumar, Kamal; Waldmann, Herbert
- Abstract
Biology-oriented synthesis employs the structural information encoded in complex natural products to guide the synthesis of compound collections enriched in bioactivity. The trans-hydrindane dehydro-δ-lactone motif defines the characteristic scaffold of the steroid-like withanolides, a plant-derived natural product class with a diverse pattern of bioactivity. A withanolide-inspired compound collection was synthesized by making use of three key intermediates that contain this characteristic framework derivatized with different reactive functional groups. Biological evaluation of the compound collection in cell-based assays that monitored biological signaltransduction processes revealed a novel class of Hedgehog signaling inhibitors that target the protein Smoothened.
- Subjects
CHEMICAL synthesis; INDAN; LACTONES; WITHANOLIDES; BOTANICAL chemistry
- Publication
Angewandte Chemie, 2015, Vol 127, Issue 19, p5688
- ISSN
0044-8249
- Publication type
Article
- DOI
10.1002/ange.201500112