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.
Bioorganic & medicinal chemistry letters. 2016 Jun 11 [Epub ahead of print]
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
College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea., College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea., Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 136-702, Republic of Korea., College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea., College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea., College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea., College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea., College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea., Department of Beauty Science, Kwangju Women's University, Kwangju 506-713, Republic of Korea., College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea., Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 136-702, Republic of Korea. Electronic address: ., College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea. Electronic address: .