Prediction and evaluation of the lipase inhibitory activities of tea polyphenols with 3D QSAR models
The extraordinary hypolipidemic effects of polyphenolic compounds from tea have been confirmed in our previous study. To gain compounds with more potent activities, using the conformations of the most active compound revealed by molecular docking, a 3D QSAR pancreatic lipase inhibitor model with good predictive ability was established and validated by CoMFA and CoMISA methods. With good statistical significance in CoMFA (r2cv 0.622, r2 0.956, F 261.463, SEE 0.096) and CoMISA (r2cv 0.631, r2 0.932, F 75.408, SEE 0.212) model, we summarized the structure activity relationship between polyphenolic compounds and pancreatic lipase inhibitory activities and find the bulky substituents in R2, R4 and R5, hydrophilic substituents in R1 and electron withdrawing groups in R2 are the key factors to enhance the lipase inhibitory activities. Under the guidance of the 3D QSAR results, (2R,3R,2'R,3'R) desgalloyloolongtheanin 3,3' O digallate (DOTD) a potent lipase inhibitor with an IC50 of 0.08 mg/ml, was obtained from EGCG oxidative polymerization catalyzed by crude polyphenol oxidase. Furthermore, DOTD was found to inhibit lipid absorption in olive oil loaded rats, which was related with inhibiting the activities of lipase in the intestinal mucosa and contents.
Scientific reports