袁雷,杨元帅,王志强,王健,孙铁民
YUAN Lei,YANG Yuan-shuai,WANG Zhi-qiang,WANG Jian,SUN Tie-min(Key Laboratory of Structure-Based Drug Design & Discovery

• 1:沈阳药科大学基于靶点的药物设计与研究教育部重点实验室

摘要(Abstract)：

目的基于"天然产物共同药效团"策略探讨天然产物patriscabratine作用靶点,为其深入研究奠定基础。方法通过分子力场分析方法,初步确定与patriscabratine药效结构相似的天然产物aurantiamide acetate为模板分子,鉴于aurantiamide acetate是通过抑制组织蛋白酶L发挥的抗肿瘤活性,进一步基于组织蛋白酶L的晶体结构,利用分子对接方法,探讨两种天然产物与活性腔的作用模式并进行比对。进一步通过抗肿瘤活性验证计算结果。结果与结论经LigandScout软件分析表明两种天然产物作用方式基本一致,抗肿瘤活性结果表明二者的半数抑制浓度相似。初步确定patriscabratine的作用靶点为组织蛋白酶L。
Objective To investigate the target of patriscabratine based on a natural product consensus pharmacophore strategy for laying the foundation for further study.Methods By molecular field-based similarity analysis,aurantiamide acetate was determined as model molecule with a similar pharmacophore to patriscabratine.As well known,the target of aurantiamide acetate is cathepsin L.Starting from the crystals structure of cathepsin L,molecular docking studies were used to analyze and compare the interactions between patriscabratine and aurantiamide acetate and cathepsin L.Antitumor activity checked the computation results furtherly.Results and Conclusions The two natural products share similar interaction modes.Antitumor activity evaluation showed the IC50 value of patriscabratine was approximate to that of aurantiamide acetate.These results obtained in this paper indicate primarily the target of patriscabratine is cathepsin L.

关键词(KeyWords)： 天然产物共同药效团;patriscabratine;aurantiamide acetate;分子对接;分子力场;抗肿瘤活性
natural product consensus pharmacophore strategy;patriscabratine;aurantiamide acetate;molecular docking;molecular field;antitumor activity

Abstract:

Keywords:

基金项目(Foundation): 高等学校博士学科点专项科研基金新教师类资助课题(41310819);; 辽宁省教育厅资助课题(L2011174)

作者(Author): 袁雷,杨元帅,王志强,王健,孙铁民
YUAN Lei,YANG Yuan-shuai,WANG Zhi-qiang,WANG Jian,SUN Tie-min(Key Laboratory of Structure-Based Drug Design & Discovery

DOI: 10.14066/j.cnki.cn21-1349/r.2012.11.009

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