计算机辅助药物设计筛选鞘氨醇激酶1型抑制剂  

Screening of SphK1 inhibitors based on computer aided drug design

作　　者：苟渟婷 冯蓉 何俊[3] 师健友[4] 许建[4] 龚军[4] 叶强[1] GOU Tingting;FENG Rong;HE Jun;SHI Jianyou;XU Jian;GONG Jun;YE Qiang(State Key Laboratory of Southwestern Chinese Medicine Resources,Department of Pharmacy,Chengdu University of TCM,Sichuan,611137 P.R.China;Yunnan Maternal and Child Health Hospital,Kunming,Yunnan,650051 P.R.China;West China School of Pharmacy,Sichuan University,Chengdu,Sichuan,610041 P.R.China;Sichuan Provincial People′s Hospital,Chengdu,Sichuan,610031 P.R.China)

机构地区：[1]成都中医药大学药学院西南特色中药资源国家重点实验室,四川成都611137 [2]云南省妇幼保健院,云南昆明650051 [3]四川大学华西药学院,四川成都610041 [4]四川省人民医院,四川成都610031

出　　处：《华西药学杂志》2024年第6期649-654,共6页West China Journal of Pharmaceutical Sciences

基　　金：西南特色中药资源国家重点实验室开放基金(2021HX026);四川省科技计划项目(2022YFS0224)。

摘　　要：目的寻找和发现具有新骨架的鞘氨醇激酶1型(SphK1)抑制剂,并预测其活性。方法采用药效团模型和分子对接虚拟筛选ChemDiv数据库,得到排序靠前的化合物,并通过定量构效关系(QSAR)模型预测其活性。结果得到6个化合物,其Fit value值和分子对接打分均接近或高于阳性对照化合物;QSAR模型预测其对SphK1具有潜在抑制效力。结论获得6个具有新骨架结构的小分子抑制剂,为开发靶向SphK1的小分子抑制剂具有重要意义。OBJECTIVE To search and discover sphingosine kinase type 1(SphK1)inhibitors with new scaffolds,and to predict their activity.METHODS Pharmacophore model and molecular docking virtual screening ChemDiv database were used to obtain the top ranking compounds,and their activities were predicted by quantitative structure-activity relationship(QSAR)model.RESULTS Six compounds with Fit values and molecular interface scores close to or higher than positive control compounds were obtained.The QSAR model predicted that they had potential inhibitory effect on SphK1.CONCLUSION Six compounds with novel scaffold structures have been obtained,which can provide lead compounds for the development of SphK1 inhibitors.

关 键 词：鞘氨醇激酶1型 小分子抑制剂 计算机辅助药物设计 药效团模型 定量构效关系 广义波恩表面积模型 ADMET预测 虚拟筛选 分子对接 

分 类 号：R96[医药卫生—药理学]