Anticoagulant activity screening of an in-house database of natural compounds for discovering novel selective factor Xa inhibitors; a combined in silico and in vitro approach

摘要

Traditional edible natural products enclose a wealth of anticoagulants that can be prospected for new selective factor Xa inhibitors. Unlike multitargeted anticoagulants, selective factor Xa inhibitors effectively block coagulation cascade with a broader therapeutic window. In the present study, an in-house database comprises 3D structures of 1571 compounds from 26 natural products previously reported to enhance the bleeding tendency was compiled. Virtual screening (VS) of the constructed database to discover active FXa inhibitors was performed using sequential structure-based VS by Glide extra precision docking followed by ligand-based VS through pharmacophore modeling and 3D-QSAR. The implemented approach provoked liquorice, trifolium and olive as candidates for chromogenic in vitro FXa inhibitory assay with IC50 values of 0.363, 0.729, and 0.866 mg/mL, respectively. Evaluation of liquorice solvent fractions revealed that ethyl acetate fraction produced 97.93 +/- 0.019% inhibition of FXa. The adopted integrated strategy can be implemented for isolation of potent, selective nature-based FXa inhibitors.