Naturally occurring FANCF-Hes1 complex inhibitors from Wrightia religiosa

Midori A. Arai; Kenji Uemura; Nozomi Hamahiga; Naoki Ishikawa; Takashi Koyano; Thaworn Kowithayakorn; Tagrid Kaddar; Madeleine Carreau; Masami Ishibashi

doi:10.1039/c4md00495g

Naturally occurring FANCF-Hes1 complex inhibitors from Wrightia religiosa

Midori A. Arai, Kenji Uemura, Nozomi Hamahiga, Naoki Ishikawa, Takashi Koyano, Thaworn Kowithayakorn, Tagrid Kaddar, Madeleine Carreau, Masami Ishibashi

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

10 Citations (Scopus)

Abstract

The isolation and evaluation of inhibitors of Fanconi F protein (FANCF)-hairy and enhancer of split 1 (Hes1) complex are described. A high-throughput screening assay for small-molecule inhibitors of the FANCF-Hes1 complex was realized. Successful complex formation between fluorophore (Cy3)-labeled human FANCF and immobilized rat or human HES1 on a microplate was established. Screening of our plant extract library using this system resulted in the isolation of eight natural products, including two new flavonoid glycosides (3 and 4), from Wrightia religiosa. Of these compounds, 3, 5, and 7 showed potent inhibition of the FANCF-Hes1 complex formation. Compound 7 disrupted the FANCF-Hes1 complex more efficiently than the Hes1 dimer.

Original language	English
Pages (from-to)	455-460
Number of pages	6
Journal	MedChemComm
Volume	6
Issue number	3
DOIs	https://doi.org/10.1039/c4md00495g
Publication status	Published - 2015 Mar 1
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Pharmacology
Pharmaceutical Science
Drug Discovery
Organic Chemistry

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title = "Naturally occurring FANCF-Hes1 complex inhibitors from Wrightia religiosa",

abstract = "The isolation and evaluation of inhibitors of Fanconi F protein (FANCF)-hairy and enhancer of split 1 (Hes1) complex are described. A high-throughput screening assay for small-molecule inhibitors of the FANCF-Hes1 complex was realized. Successful complex formation between fluorophore (Cy3)-labeled human FANCF and immobilized rat or human HES1 on a microplate was established. Screening of our plant extract library using this system resulted in the isolation of eight natural products, including two new flavonoid glycosides (3 and 4), from Wrightia religiosa. Of these compounds, 3, 5, and 7 showed potent inhibition of the FANCF-Hes1 complex formation. Compound 7 disrupted the FANCF-Hes1 complex more efficiently than the Hes1 dimer.",

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T1 - Naturally occurring FANCF-Hes1 complex inhibitors from Wrightia religiosa

AU - Arai, Midori A.

AU - Uemura, Kenji

AU - Hamahiga, Nozomi

AU - Ishikawa, Naoki

AU - Koyano, Takashi

AU - Kowithayakorn, Thaworn

AU - Kaddar, Tagrid

AU - Carreau, Madeleine

AU - Ishibashi, Masami

PY - 2015/3/1

Y1 - 2015/3/1

N2 - The isolation and evaluation of inhibitors of Fanconi F protein (FANCF)-hairy and enhancer of split 1 (Hes1) complex are described. A high-throughput screening assay for small-molecule inhibitors of the FANCF-Hes1 complex was realized. Successful complex formation between fluorophore (Cy3)-labeled human FANCF and immobilized rat or human HES1 on a microplate was established. Screening of our plant extract library using this system resulted in the isolation of eight natural products, including two new flavonoid glycosides (3 and 4), from Wrightia religiosa. Of these compounds, 3, 5, and 7 showed potent inhibition of the FANCF-Hes1 complex formation. Compound 7 disrupted the FANCF-Hes1 complex more efficiently than the Hes1 dimer.

AB - The isolation and evaluation of inhibitors of Fanconi F protein (FANCF)-hairy and enhancer of split 1 (Hes1) complex are described. A high-throughput screening assay for small-molecule inhibitors of the FANCF-Hes1 complex was realized. Successful complex formation between fluorophore (Cy3)-labeled human FANCF and immobilized rat or human HES1 on a microplate was established. Screening of our plant extract library using this system resulted in the isolation of eight natural products, including two new flavonoid glycosides (3 and 4), from Wrightia religiosa. Of these compounds, 3, 5, and 7 showed potent inhibition of the FANCF-Hes1 complex formation. Compound 7 disrupted the FANCF-Hes1 complex more efficiently than the Hes1 dimer.

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Naturally occurring FANCF-Hes1 complex inhibitors from Wrightia religiosa

Abstract

ASJC Scopus subject areas

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