2. Academic Validation
  3. Linderapyrone: A Wnt signal inhibitor isolated from Lindera umbellata

Linderapyrone: A Wnt signal inhibitor isolated from Lindera umbellata

  • Bioorg Med Chem Lett. 2021 Aug 1:45:128161. doi: 10.1016/j.bmcl.2021.128161.
Takahiro Matsumoto 1,  Takahiro Kitagawa 2,  Daisuke Imahori 2,  Atsushi Matsuzaki 2,  Youhei Saito 2,  Tomoe Ohta 3,  Tatsusada Yoshida 3,  Yuji Nakayama 2,  Eishi Ashihara 2,  Tetsushi Watanabe 4
Affiliations

Affiliations

  • 1 Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan. Electronic address: tmatsumo@mb.kyoto-phu.ac.jp.
  • 2 Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
  • 3 Nagasaki International University, Nagasaki 859-3298, Japan.
  • 4 Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan. Electronic address: watanabe@mb.kyoto-phu.ac.jp.
PMID: 34062253 DOI: 10.1016/j.bmcl.2021.128161
Abstract

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).

Keywords

DNA microarray analysis; Lindera umbellata; Linderapyrone; TCF/β-catenin transcriptional activity; Wnt signal.

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