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Natural products isolation using protein based methods is an attractive for obtaining bioactive compounds. To discover neural stem cell (NSC) differentiation activators, we isolated eight inhibitors of Hes1 dimer formation from  Psidium guajava  using the Hes1-Hes1 interaction fluorescent plate assay and one inhibitor from  Terminalia chebula  using the Hes1-immobilized beads method. Of the isolated compounds, gallic acid ( 8 ) and 4- O -(4”- O -galloyl-α-L-rhamnopyranosyl)ellagic acid ( 11 ) showed potent Hes1 dimer formation inhibitory activity, with IC 50  values of 10.3 and 2.53 μM, respectively. Compound  11  accelerated the differentiation activity of C17.2 NSC cells dose dependently, increasing the number of neurons with a 125% increase (5 μM) compared to the control.

Target protein-oriented isolation of Hes1 dimer inhibitors using protein based methods