Pharmacophore modelling and 3D-QSAR studies on antithrombotic activity of biphenyl analogues

Thrombin regulates blood coagulation and has a central role in haemostasis. Antithrombotic compounds such as biphenyl derivatives are known to target thrombin and can significantly treat thrombosis-related disorders. In this communication we describe in silico methods such as generation of common pharmacophore hypothesis and 3D-QSAR model, based on the structural features of biphenyl derivatives. The best pharmacophore hypothesis generated consists of three features, namely two aromatic rings (R), two hydrogen donors (D) and one positive ionizable group (P). To validate common pharmacophore and 3D-QSAR models, biphenyl derivatives were docked against the available 3D structure of thrombin (PDB: 2C8W), which gave the best scoring and interactions with compound 4. The statistically validated 3D-QSAR illustrates good predictability values and root mean square error. Our finding helps identify the structure- activity relationship of biphenyl derivatives against thrombin.