Naturally occurring FANCF-Hes1 complex inhibitors from Wrightia religiosa

The isolation and evaluation of inhibitors of Fanconi F protein (FANCF) - haity 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.