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.

中文翻译：

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内部天然化合物数据库的抗凝活性筛选，用于发现新型选择性因子Xa抑制剂；计算机和体外相结合的方法

传统的食用天然产品包含大量的抗凝剂，可用于新型选择因子Xa抑制剂。与多靶点抗凝剂不同，选择性因子Xa抑制剂可在更宽的治疗范围内有效阻断凝血级联反应。在本研究中，对内部数据库进行了汇总，该数据库包含来自26种天然产物的1571种化合物的3D结构，先前报道有26种天然产物可增强出血趋势。使用Glide超精密对接基于顺序结构的VS，然后通过药效基团建模和3D-QSAR，基于配体的VS，对构建的数据库进行虚拟筛选（VS）以发现活性FXa抑制剂。实施的方法激怒了甘草，三叶草和橄榄可作为发色体外FXa抑制试验的候选物，IC ₅₀值分别为0.363、0.729和0.866 mg / mL。对甘草溶剂馏分的评估表明，乙酸乙酯馏分对FXa的抑制作用为97.93±0.019％。可以采用所采用的整合策略来分离有效的，选择性的，基于性质的FXa抑制剂。