Evaluation of the Sedative Effect of the Phytochemicals from Hyoscyamus Genus Using the Molecular Docking and QSAR Analyses

Abstract

Medicinal plants as a rich source of different bioactive constituents, have been traditionally used for treatment of different disease, since a long time. Hyoscyamus genus has also been regarded as an important medical plant due to its anti-cancer, antioxidant, anti-diabetic, anti-parkinson, anti-spasmodic, pain relief and sedative activities [1, 2]. Molecular docking and QSAR analyses, as the most widely used strategies in computer- assisted drug design, play a major role for the identification of suitable molecular scaffold and distinguishing selectivity for the target proteins [3]. Herein, the over- mentioned in silico assays were applied to evaluate the sedative effect of the plants of Hyoscyamus genus through the inhibition of the activity of GABAa receptors. For this, reported chemical constituents of the Hyoscyamus genus was collected from the literature and then their sedative effect was determined against two sub-unites of GABAa with the PDB codes of 6D6T and 4COF. Results of molecular docking analysis revealed a good affinity, activity and binding orientation of some ligands to the target proteins. Based on the obtained results, compound 7ß-hydroxyhyoscyamine had the best affinity to the target proteins of 6D6T and 4COF with docking score values of -6.291 and -5.513 kcal/mol respectively. In continue, pharmacophore modelling and 3D-QSAR studies were performed on a dataset of 30 sedative drugs with the intention of exploring entry inhibitors with better therapeutic potential. The common pharmacophore hypothesis of AARRR was used for 3D-QSAR model development, which indicated the predicted activity of 0.622 nM for compound 7ß-hydroxy hyoscyamine, confirming the results of molecular docking analysis.