title: Synthesis and evaluation of (+)-decursin derivatives as inhibitors of the Wnt/β-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/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.
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Jee-Hyun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Min-Ah
authors.initials: MA
authors.lastname: Kim
authors.affiliation: Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 136-702, Republic of Korea.
authors.forename: Seoyoung
authors.initials: S
authors.lastname: Park
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Soo-Hyun
authors.initials: SH
authors.lastname: Cho
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Eunju
authors.initials: E
authors.lastname: Yun
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Yu-Seok
authors.initials: YS
authors.lastname: O
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Jiseon
authors.initials: J
authors.lastname: Kim
authors.affiliation: College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Ja-Il
authors.initials: JI
authors.lastname: Goo
authors.affiliation: Department of Beauty Science, Kwangju Women's University, Kwangju 506-713, Republic of Korea.
authors.forename: Mi-Young
authors.initials: MY
authors.lastname: Yun
authors.affiliation: College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Yongseok
authors.initials: Y
authors.lastname: Choi
authors.affiliation: Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 136-702, Republic of Korea. Electronic address: ohsa@kookmin.ac.kr.
authors.forename: Sangtaek
authors.initials: S
authors.lastname: Oh
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea. Electronic address: gysong@cnu.ac.kr.
authors.forename: Gyu-Yong
authors.initials: GY
authors.lastname: Song
mesh_terms: D001578:Benzopyrans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002087:Butyrates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D006801:Humans; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D051153:Wnt Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051176:beta Catenin / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D001578:Benzopyrans; D002087:Butyrates; D051153:Wnt Proteins; D051176:beta Catenin; C101278:decursin
keywords: Cinnamoyl decursin; Phenylpropionyl decursin; Prostate cancer; Protein degradation; Wnt/β-catenin pathway