基于分子对接的咪唑啉类α_(2A)-肾上腺素能配体三维定量构效关系研究

3D QSAR of Imidazoline-derived α_(2A)-Adrenergic Ligands on the Basis of Molecular Docking

对系列咪唑啉类α2A-肾上腺素能配体类似物进行MFA和CoMFA两种方法的定量构效关系研究。化合物的构象采用与α2A-肾上腺素能受体分子对接的最佳结合构象,计算结果表明,两种方法的计算结果有较好的一致性。MFA模型的r2和xv_r2分别为0.997和0.946,CoMFA模型的r2和xv_r2分别为0.999和0.580,两种方法得到的定量构效关系模型均有较好的拟合能力和预测能力,可用于对咪唑啉类α2A-肾上腺素能配体化合物进行虚拟筛选和活性评价。研究结果为进一步设计合成新的候选化合物提供理论依据。

On the basis of binding conformation,the three-dimensional structure-activity relationships of imidazoline-derived α2A-adrenergic ligands were studied by using CoMFA and MFA technique. The results showed that the built two 3D QSAR models were significant and had good predictability. The r2 and XV-r2 were 0. 997 and 0. 946 for MFA model and 0. 999 and 0. 580 for CoMFA model,respectively. The obtained models can be used to virtual screening and prediction activities for imidazoline-derived α2A-adrenergic ligands compounds. Moreover,the established the QSAR models of imidazoline-derived α2A-adrenergic ligands can give insights to the further design and synthesize of the new lead compounds.