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

doi:10.1016/j.bmcl.2016.06.029

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

Department of Biotechnology

Research output: Contribution to journal › Article › peer-review

6 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 language	English
Pages (from-to)	3529-3532
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	26
Issue number	15
DOIs	https://doi.org/10.1016/j.bmcl.2016.06.029
Publication status	Published - 2016

Bibliographical note

Funding Information:
This study was supported by Basic Science Research Program ( NRF-2013R1A1A2062764 , 2015R1A2A2A01004599 ) through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, Education and Technology and by the Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 2009-0093815 ).

Publisher Copyright:
© 2016

Keywords

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

ASJC Scopus subject areas

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmcl.2016.06.029

Cite this

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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.",

keywords = "Cinnamoyl decursin, Phenylpropionyl decursin, Prostate cancer, Protein degradation, Wnt/β-catenin pathway",

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

note = "Funding Information: This study was supported by Basic Science Research Program ( NRF-2013R1A1A2062764 , 2015R1A2A2A01004599 ) through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, Education and Technology and by the Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 2009-0093815 ). Publisher Copyright: {\textcopyright} 2016",

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doi = "10.1016/j.bmcl.2016.06.029",

language = "English",

volume = "26",

pages = "3529--3532",

journal = "Bioorganic and Medicinal Chemistry Letters",

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T1 - Synthesis and evaluation of (+)-decursin derivatives as inhibitors of the Wnt/β-catenin pathway

AU - Lee, Jee Hyun

AU - Kim, Min Ah

AU - Park, Seoyoung

AU - Cho, Soo Hyun

AU - Yun, Eunju

AU - O, Yu Seok

AU - Kim, Jiseon

AU - Goo, Ja Il

AU - Yun, Mi Young

AU - Choi, Yongseok

AU - Oh, Sangtaek

AU - Song, Gyu Yong

N1 - Funding Information: This study was supported by Basic Science Research Program ( NRF-2013R1A1A2062764 , 2015R1A2A2A01004599 ) through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, Education and Technology and by the Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 2009-0093815 ). Publisher Copyright: © 2016

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

KW - Cinnamoyl decursin

KW - Phenylpropionyl decursin

KW - Prostate cancer

KW - Protein degradation

KW - Wnt/β-catenin pathway

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AN - SCOPUS:84977487608

SN - 0960-894X

VL - 26

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EP - 3532

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 15

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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