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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 explore the target of natural product patriscabratine based on the strategy of “common product of natural products” to lay the foundation for its further study. METHODS: Aurantiamide acetate, a natural product analogous to the pharmacodynamic structure of patriscabratine, was initially identified as a template molecule by molecular force field analysis. Given that aurantiamide acetate exerts its antitumor activity by inhibiting cathepsin L, it is further based on the crystal structure of cathepsin L Molecular docking method to explore the interaction between the two natural products and the active cavity mode and compare. Further validation of anti-tumor activity calculated results. RESULTS AND CONCLUSIONS Analysis by LigandScout software showed that the two natural products behaved basically in the same way. The anti-tumor activity results showed that the two half-inhibitory concentrations were similar. Preliminary identification of the target of patriscabratine is cathepsin L.