2-苯氧茚酮类乙酰胆碱酯酶抑制剂的3D-QSAR研究(英文)

3D-QSAR studies on AChE inhibitory activities of 2-phenoxy-indan-1-one derivatives

目的研究2-苯氧茚酮类乙酰胆碱酯酶抑制剂的三维定量构效关系。方法采用比较分子力场分析法(CoMFA)和比较分子相似性指数分析法(CoMSIA)对结构与活性的关系进行研究。结果CoMFA模型表明立体场和静电场对活性的贡献分别为0.805和0.195;CoMSIA模型阐明疏水场和氢键场对活性也有一定的影响。结论两种3D-QSAR模型都显示出相当高的预测能力,CoMFA和CoMSIA的交叉验证值q2分别为0.881和0.918,通过对两种3D-QSAR模型等势图的分析,可为开展进一步的药物设计和结构优化提供理论指导和依据。

Aim To study the 3D-QSAR of 2-phenoxy-indan-1-one derivatives bearing AChE inhibitory activities. Methods Comparative molecular field analysis （CoMFA） and comparative molecular similarity indices analysis （CoMSIA） were used. Results The results show that the contributions of steric and electrostatic fields to the activity with CoMFA model are 0. 805 and 0.195, respectively. Addition of CoMSIA study has elucidated the role of hydrophobic and hydrogen bonding along with the effect of steric and electrostatic properties revealed by CoMFA. Conclusion The two 3D-QSAR model have demonstrated a good fit, the analysis of CoMFA and CoMSIA contour maps provided insight into the possible modification of the molecules with better activity.