Combined 3D‐QSAR Modeling and Molecular Docking Study on Quinoline Derivatives as Inhibitors of P‐selectin

P‐selectin is a promising target for developing novel atherosclerosis drugs. To understand the structure–activity correlation of quinolines‐based P‐selectin inhibitors, we have carried out a combined molecular docking and three‐dimensional quantitative structure–activity relationship (3D‐QSAR) modeling study. The study has resulted in two types of satisfactory 3D‐QSAR models, including the CoMFA model (r², 0.863; q², 0.589) and CoMSIA model (r², 0.866; q², 0.636), to predict the biological activity of new compounds. The detailed microscopic structures of P‐selectin binding with inhibitors have been studied by molecular docking. We have also developed docking based 3D‐QSAR models (CoMFA with r², 0.934; q², 0.591; CoMSIA with r², 0.896; q², 0.573). The contour maps obtained from the 3D‐QSAR models in combination with the docked binding structures help to better interpret the structure–activity relationship. All of the structural insights obtained from both the 3D‐QSAR contour maps and molecular docking are consistent with the available experimental activity data. The satisfactory results strongly suggest that the developed 3D‐QSAR models and the obtained P‐selectin‐inhibitor binding structures are reasonable for the prediction of the activity of new inhibitors and in future drug design.