Linderapyrone: A Wnt signal inhibitor isolated from Lindera umbellata
| Autor: | Tatsusada Yoshida, Youhei Saito, Tomoe Ohta, Yuji Nakayama, Eishi Ashihara, Takahiro Kitagawa, Takahiro Matsumoto, Atsushi Matsuzaki, Daisuke Imahori, Tetsushi Watanabe |
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| Rok vydání: | 2021 |
| Předmět: |
Monoterpene
Clinical Biochemistry Cell Pharmaceutical Science 01 natural sciences Biochemistry Structure-Activity Relationship chemistry.chemical_compound Complementary DNA Drug Discovery medicine Humans Bioassay Luciferase Wnt Signaling Pathway Molecular Biology beta Catenin Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Chemistry Organic Chemistry Wnt signaling pathway Lindera Molecular biology Pyrone 0104 chemical sciences 010404 medicinal & biomolecular chemistry medicine.anatomical_structure Molecular Medicine TCF Transcription Factors Piperitone |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 45:128161 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2021.128161 |
| Popis: | Linderapyrone, a Wnt signal inhibitor was isolated from the methanolic extract of the stems and twigs of Lindera umbellata together with epi-(-)-linderol A. Linderapyrone inhibited TCF/β-catenin transcriptional activity that was evaluated using cell-based TOPFlash luciferase assay system. To evaluate the structure-activity relationship and mechanism, we synthesized linderapyrone and its derivatives from piperitone. As the results of further bioassay for synthesized compounds, we found both of pyrone and monoterpene moieties were necessary for inhibitory effect. cDNA microarray analysis in a linderapyrone derivative treated human colorectal cancer cells showed that this compound downregulates Wnt signaling pathway. Moreover, we successes to synthesize the derivative of linderapyrone that has stronger inhibitory effect than linderapyrone and ICG-001 (positive control). |
| Databáze: | OpenAIRE |
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