Exploration of Potential Targets of Phenolic Extracts from the Twigs of Cinnamomum Cassia<\i>

OBJECTIVE To discovery the potential target of lignans， phenolic extracts from the twigs of Cinnamomum cassia. METHODS Firstly， hypothesis which matched the lignan derivative with the FitValue greater than 0.75 were selected from the pharmacophore model database. Secondly， the lignan derivative was inverse docked to the target proteins which these pharmacophore models selected from. Thirdly， the protein with the best docking result was chosen to build the 3D-QSAR pharmacophore model using their reported inhibitors to predict the potency of the lignan derivative. The binding force of compound 1 with Tankyrase 1 was tested by fluorescence polarization. The content of Tankyrase 1 in cells after adding compound 1 was tested by Western blot. Finally， the interactions between the lignan derivative and target protein were obtained by molecular dynamics simulation. RESULTS Seventeen pharmacophore models matched the lignan derivative with the FitValue greater than 0.75. Four of them belonged to neuroprotective targets with a highest proportion up to 24%. Inverse docking results showed that the binding energy (E=-65 kcal/mol) between the lignan derivative and the Tankyrase 1 protein (PDB ID: 4TOR) was the lowest. In addition， the predicted potency of the compound was 0.61 μmol/L， the Ki of compound and Tankyrase 1 protein was （0.15±0.01）μmol/L， a moderate inhibition. Western blot showed that compound 1 could decrease the expression of Tankyrase 1 protein in SW480 cells. Molecular dynamics results showed that the interactions between the lignan derivative and 4TOR were similar to that between the reported inhibitor and 4TOR. CONCLUSION After inverse targeting of the phenolic extracts from the Twigs Cinnamomum cassia lignan derivative and the activity test， lignan derivative potentially inhibited against Tankyrase 1.