化学学报 ›› 2009, Vol. 67 ›› Issue (19): 2258-2268. 上一篇    

研究论文

5-羟色胺(5-HT)和去甲肾上腺素(NE)重摄取抑制剂药效团模型的建立及比较分析

秦芳   郭彦伸    文辉   杨光中   

  1. (北京协和医学院 中国医学科学院药物研究所 北京 100050)
  • 收稿日期:2008-09-16 修回日期:2008-12-30 出版日期:2009-10-14 发布日期:2009-06-07
  • 通讯作者: 杨光中
  • 基金资助:

    国家自然科学基金(批准号:30572233);北京市自然科学基金(批准号:7062045)资助

Pharmacophore Identidification and Comparison of Serotonin/Norepinephrine Reuptake Inhibitors

Qin, Fang       Guo, Yanshen      Wen, Hui      Yang, Guangzhong   

  1. (Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050)
  • Received:2008-09-16 Revised:2008-12-30 Online:2009-10-14 Published:2009-06-07

近年来的研究表明, 去甲肾上腺素(NE)能系统和5-羟色胺(5-HT)能系统可能共同参与了抑郁症的发病机制. 采用Catalyst软件的Hypogen方法, 利用22个不同结构类型的5-HT重摄取抑制剂和19个不同结构类型和活性的NE重摄取抑制剂分别建立了5-HT药效团模型和NE药效团模型, 它们的相关系数分别为0.935, 0.844, 这表明所得到的模型能较好地表征重摄取抑制剂化合物的特征; 此外, 我们还选择了四种不同活性的预测集分别对所建立的药效团模型进行检验, 结果表明所建立的药效团模型具有较好的预测能力. 对这两个药效团模型进行了比较分析, 其结果可以为设计高活性的双重5-HT和NE重摄取抑制剂提供依据.

关键词: 5-羟色胺, 去甲肾上腺素, 药效团模型, 双重重摄取抑制剂

The biogenic amine transmitters serotonin and norepinephrine have been linked to depression. Pharmacophore models were developed by using Catalyst Hypogen program with a training set of 22 5-HT reuptake inhibitors and 19 NE reuptake inhibitors, which were carefully selected with great diversity in both molecular structure and bioactivity for discovering new potent serotonin/norepinephrine reuptake inhibitors. The best 5-HT pharmacophore hypothesis (Hypo1), has a correlation coefficient of 0.935. The best NE pharmacophore hypothesis (Hypo1), has a correlation coefficient of 0.844, suggesting that a highly predictive 5-HT and NE pharmacophore models were successfully obtained. The predictive ability was approved by the results of the activity estimated by mapping the compounds of the training and testing sets with pharmacophore models. The results of our study provide a valuable tool in designing new leads with desired biological activity by virtual screening.

Key words: serotonin, norepinephrine, pharmacophore model, dual reuptake inhibitors