Synthesis and evaluation of (+)-decursin derivatives as inhibitors of the Wnt/β-catenin pathway

Jee Hyun Lee, Min Ah Kim, Seoyoung Park, Soo Hyun Cho, Eunju Yun, Yu Seok O, Jiseon Kim, Ja Il Goo, Mi Young Yun, Yongseok Choi, Sangtaek Oh, Gyu Yong Song

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

We synthesized (+)-decursin derivatives substituted with cinnamoyl- and phenyl propionyl groups originating from (+)-CGK062 and screened them using a cell-based assay to detect relative luciferase reporter activity. Of this series, compound . 8b, in which a 3-acetoxy cinnamoyl group was introduced, most potently inhibited (97.0%) the Wnt/β-catenin pathway. Specifically, compound . 8b dose-dependently inhibited Wnt3a-induced expression of the β-catenin response transcription (CRT) and increased β-catenin degradation in HEK293 reporter cells. Furthermore, compound . 8b suppressed expression of the downstream β-catenin target genes cyclin D1 and c-myc and suppressed PC3 cell growth in a concentration-dependent manner.

Original languageEnglish
JournalBioorganic and Medicinal Chemistry Letters
DOIs
Publication statusAccepted/In press - 2015 Nov 4

Keywords

  • Cinnamoyl decursin
  • Phenylpropionyl decursin
  • Prostate cancer
  • Protein degradation
  • Wnt/β-catenin pathway

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Fingerprint Dive into the research topics of 'Synthesis and evaluation of (+)-decursin derivatives as inhibitors of the Wnt/β-catenin pathway'. Together they form a unique fingerprint.

  • Cite this

    Lee, J. H., Kim, M. A., Park, S., Cho, S. H., Yun, E., O, Y. S., Kim, J., Goo, J. I., Yun, M. Y., Choi, Y., Oh, S., & Song, G. Y. (Accepted/In press). Synthesis and evaluation of (+)-decursin derivatives as inhibitors of the Wnt/β-catenin pathway. Bioorganic and Medicinal Chemistry Letters. https://doi.org/10.1016/j.bmcl.2016.06.029