目的 建立一种基于谱效-构效结合的高效天然化合物活性筛选体系，并采用该体系筛选大黄中酪氨酸酶抑制剂。方法 根据酪氨酸酶催化底物发生反应的原理，以大黄为例依次经过不同极性溶剂提取，分别检测各极性提取物对酪氨酸酶活性的抑制作用；针对活性组分通过UPLC-Q/TOF鉴定活性成分，采用计算机辅助药物设计评价构效关系，进一步筛选抑制剂分子，并结合酶学检测验证药效成分。结果 通过建立的谱效-构效结合筛选体系获得大黄中大黄素、藜芦酚-4′-O-β-D-葡萄糖苷等9种具有间二羟基苯酚、邻三羟基苯酚结构的化合物可能具有酪氨酸酶活性抑制作用。结论 大黄中大黄素和藜芦酚衍生物对酪氨酸酶活性具有明显的抑制作用；谱效-构效相结合的筛选模式为天然化合物活性筛选提供了便捷方法。

Objective To establish a new efficient screening system based on spectrum-efficiency-structure-activity relationship of natural compounds and to screen tyrosinase inhibitor from Rheum officinale (rhubarb). Methods Based on the catalyzing reaction of tyrosinase to its substrate, Soxhlet extraction system was used and R. officinale was extracted by solvents of different polars. The inhibitory activities on tyrosinase in different polar extract fractions were detected. UPLC-Q/TOF and computer-aided drug design were used to analyze and identify their active ingredients. Enzymological method was used to validate the active constituents. Results Through spectrum-efficiency-structure-activity relationship, nine kinds of compounds including emodin and veraphenol-4′-O-β-D- glycoside were confirmed. The structures contained functional groups of both resorcin and adjacent trihydroxyphenol which might have the inhibitory activity on tyrosinase. Conclusion The emodin and veraphenol derivatives extracted from rhubarb show the obvious inhibitory activity against tyrosinase. The spectrum-efficiency-structure-activity relationship provides a new convenient method for the researches on natural compounds.

国家自然科学基金资助项目（81173638，81102835）