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Keywords:

  • 3D-QSAR;
  • CoMFA;
  • CoMSIA;
  • docking;
  • inhibitor;
  • 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.