Abstract

Three-dimensional quantitative structure-activity relationships were studied on 35 natural aurone derivatives by the Topomer CoMFA method to establish the 3 D-QSAR models, and exerting potent affections as Qo site inhibitors in cytochrome b activity for anti-malaria. The cross-validated q² value of the Topmer CoMFA model = 0.539, the non-cross-validated r² = 0.793, $r_{\mathit{pred}}^2$ = 0.960, which revealed the model has good stability and predictability. The steric and electrostatic field visualization provided by the Topomer CoMFA model intuitively revealed the effects of different substituent structures. Using this information for molecule design, we theoretically obtained some new aurone derivatives as antimalarial drugs with higher activity. Furthermore, molecular docking was employed to explore the binding requirements between the ligands and the receptor protein. We obtained space relations by hydrogen bonds and hydrophobic interactions between aurone derivatives and the active site residues. The observations from these QSAR and molecular docking studies can be further used to design promising antimalarial drugs.

摘要

采用Topomer CoMFA方法对35种天然aurone衍生物进行三维定量构效关系研究，建立3D-QSAR模型，并作为Qo位点抑制剂对细胞色素b活性发挥抗疟作用。Topmer CoMFA 模型的交叉验证q ²值 = 0.539，非交叉验证r ² = 0.793，$r_{\mathit{预测}}^2$= 0.960，说明模型具有良好的稳定性和可预测性。Topomer CoMFA 模型提供的空间和静电场可视化直观地揭示了不同取代基结构的影响。利用这些信息进行分子设计，我们理论上获得了一些具有更高活性的抗疟药新的 aurone 衍生物。此外，分子对接被用来探索配体和受体蛋白之间的结合要求。我们通过氢键和 aurone 衍生物与活性位点残基之间的疏水相互作用获得了空间关系。这些 QSAR 和分子对接研究的观察结果可进一步用于设计有前景的抗疟药物。