Naturally occurring FANCF–Hes1 complex inhibitors from Wrightia religiosa
| Autor: | Nozomi Hamahiga, Tagrid Kaddar, Takashi Koyano, Midori A. Arai, Kenji Uemura, Thaworn Kowithayakorn, Madeleine Carreau, Masami Ishibashi, Naoki Ishikawa |
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| Rok vydání: | 2015 |
| Předmět: |
Pharmacology
endocrine system congenital hereditary and neonatal diseases and abnormalities Flavonoid glycosides Stereochemistry Dimer Organic Chemistry Complex formation Pharmaceutical Science Biology Biochemistry Wrightia religiosa chemistry.chemical_compound chemistry FANCF embryonic structures Drug Discovery Molecular Medicine F protein HES1 Enhancer |
| Zdroj: | MedChemComm. 6:455-460 |
| ISSN: | 2040-2511 2040-2503 |
| DOI: | 10.1039/c4md00495g |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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