天然产物共同药效团导向patriscabratine的抗肿瘤活性

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。

Antitumor activity of patriscabratine based on a natural product consensus pharmacophore strategy

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 tructure 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 indicated primarily the target of patriscabratine was cathepsin L.