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

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/ß-catenin pathway. Specifically, compound 8b dose-dependently inhibited Wnt3a-induced expression of the ß-catenin response transcription (CRT) and increased ß-catenin degradation in HEK293 reporter cells. Furthermore, compound 8b suppressed expression of the downstream ß-catenin target genes cyclin D1 and c-myc and suppressed PC3 cell growth in a concentration-dependent manner.