基于药效团与分子对接筛选丹参药材中凝血酶抑制活性成分(英文)

Identification of thrombin inhibitors from Salvia Miltiorrhiza by pharmacophore based virtual screening and molecular docking

目的:辨识丹参药材中抑制凝血酶的活性成分。方法:从中药化学成分数据库(TCMD)收集丹参药材已知的化学成分群。分别采用基于药效团与基于分子对接的方法,筛选丹参药材的化学成分群以辨识凝血酶抑制剂。结果:所建凝血酶抑制剂药效团包含7个药效特征:4个疏水基团,2个氢键给体和1个正氮中心。将所建药效团筛选丹参化学成分数据库,命中14个匹配度(QFIT)在9.0以上的化合物。分子对接结果显示,17个化合物对接得分(docking score)在6.0及以上。2种方法筛选结果相比,有8个共有化合物,部分命中化合物的凝血酶抑制活性已被相关文献所佐证。结论:基于药效团与分子对接的虚拟筛选方法可用来鉴别丹参药材中凝血酶抑制活性成分,丹参的抗凝血机制与其凝血酶抑制活性有关,该结果为进一步研究丹参作用分子机制提供参考和依据。

Objective： To quest for anticoagulation active constituents from Salvia Miltiorrhiza based on thrombin target. Methods： The chemical compounds of Salvia Miltiorrhiza were collected from Traditional Chinese Medicine Database （TCMD）. Virtual screening based on pharmacophore and molecular docking were used to identify the thrombin inhibitors from Salvia Miltiorrhiza. Results： The pharmacophore model of thrombin inhibitors established includes seven features： four hydrophobic groups, two hydrogen-bond donors and one positive nitrogen group. Then, virtual screening using the pharmacophore model was performed resulting in a hit list of 14 compounds with QFIT^9.0. Molecular docking studies hit 17 constituents with the docking score ~ 6.0. There were 8 mutual compounds both hit by pharmacophore-based and docking-based screening. Parts of the hit have been reported to have the activity of thrombin inhibition by literatures. Conclusion： Virtual screening based on pharmacophore and molecular docking can be used to identify thrombin inhibitors from Salvia Miltiorrhiza. The result indicates that the mechanism of Salvia Miltiorrhiza for anticoagulation mechanism maybe related to the thrombin inhibitory activity, and virtual screening based on pharmacophore and molecular docking approach can provide a helpful tool to identify thrombin inhibitors from Salvia Miltiorrhiza.