College of Chemical Engineering and Materials Science, Zhejiang University of Technology, Hangzhou 310014, China.
Eur J Med Chem. 2009 Nov;44(11):4367-75. doi: 10.1016/j.ejmech.2009.05.029. Epub 2009 Jun 6.
Quantitative structure-activity relationship analysis for recently synthesized aryl alkanol piperazine derivatives was studied for their antidepressant activities. The statistically significant 2D-QSAR models (r(2)>0.924, r(-CV)(2)>0.870, r(-pred)(2)>0.890) were developed using genetic function approximation (GFA) when the number of descriptors in equation was set to four, indicating the descriptors of Atype_C_6, Dipole-mag, S_sssCH and Jurs-PNSA-3 mainly influence the 5-hydroxytryptamine (5-HT) reuptake inhibition activity while the descriptors of HOMO, PMI-mag, S_sssN and Shadow-XZ may chiefly control the noradrenaline (NA) reuptake inhibition activity. The results of the 2D-QSAR models were further compared with 3D-QSAR models generated by molecular field analysis (MFA), investigating the substitutional requirements for the favorable receptor-drug interaction and providing useful information in the characterization and differentiation of their binding sites. The results derived may be useful in further designing novel antidepressants prior to synthesis.
定量构效关系分析最近合成的芳烷醇哌嗪衍生物的抗抑郁活性。使用遗传函数逼近（GFA）建立了统计学意义上的二维定量构效关系模型（r（2）>0.924，r（-CV）（2）>0.870，r（-pred）（2）>0.890），当方程中的描述符数量设置为四个时，表明 Atype_C_6、Dipole-mag、S_sssCH 和 Jurs-PNSA-3 的描述符主要影响 5-羟色胺（5-HT）再摄取抑制活性，而 HOMO、PMI-mag、S_sssN 和 Shadow-XZ 的描述符可能主要控制去甲肾上腺素（NA）再摄取抑制活性。二维定量构效关系模型的结果进一步与分子场分析（MFA）生成的三维定量构效关系模型进行了比较，研究了有利于受体-药物相互作用的取代要求，并为其结合部位的特征描述和区分提供了有用的信息。这些结果可能有助于在进一步设计新型抗抑郁药物之前进行合成。
