Translate 
Abstract
The virtual screenig of natural product databases with validated pharmacophore models is an efficient and trendsetting strategy for the discovery of bioactive compounds from natural origin [1]. Peroxisome proliferator-activated receptor α (PPARα), a ligand-activated transcription factor belonging to the nuclear hormone receptor family, regulates genes involved in fatty acid uptake and oxidation, inflammation and vascular function [2]. Fibrates, synthetic PPARα activators, are used in clinical practice as lipid-lowering agents showing a reduction in coronary heart disease risk through modification of atherogenic dyslipidemia [2]. The aim of this work is the discovery of new PPARα activators from natural sources by an in silico approach. Three pharmacophore models were generated and validated in a previous study [3]. Virtual screening of two in-house generated natural product databases, NPD (containing more than 110.000 compounds) and DIOS (containing more than 9.000 compounds from well known medicinal plants) resulted in 374 (0.34% of NPD) and 73 hits (0.75% of DIOS), respectively. Virtual hits were at first roughly divided into chemical classes. Due to the large amount of phenolic compounds, they were subdivided into further subclasses such as phenylpropanoids, lignans, flavonoid glycosides and benzofurans. Evaluation of the virtual hits within the class of phenolics showed that already 38.8% are described in literature to possess anti-inflammatory properties. These findings might act as a proof of concept since PPARα is involved in different inflammatory processes. An ongoing project is the verification of the obtained in silico results by in vitro testing of the virtual predicted activators.
Published Version
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
