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. Epub 2021 May 29.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dose-Response Relationship, Drug
  • Humans
  • Lindera / chemistry*
  • Molecular Structure
  • Structure-Activity Relationship
  • TCF Transcription Factors / antagonists & inhibitors*
  • TCF Transcription Factors / metabolism
  • Wnt Signaling Pathway / drug effects
  • beta Catenin / antagonists & inhibitors*
  • beta Catenin / metabolism

Substances

  • TCF Transcription Factors
  • beta Catenin