中草药中天然黄嘌呤氧化酶抑制剂的虚拟筛选

目的 采用药效团及文献挖掘技术，筛选中草药中天然黄嘌呤氧化酶抑制剂（xanthine oxidase inhibitor，XOI），并研究其分布情况。方法 采用基于药效团的虚拟筛选和数据挖掘技术，在23 033个中药天然产物中筛选潜在的XOI。通过吸收、分布、代谢和排泄性质及药效团初步筛选具有潜在黄嘌呤氧化酶（xanthine oxidase，XO）抑制活性的化合物；使用分子对接技术进一步筛选XOI并选取打分较高的化合物，分析作用机制；采用数据挖掘方法分析潜在XOI化合物在中草药中的分布规律。结果 通过HypoGen方法构建了XOI药效团模型，筛选得到165个潜在活性化合物。通过分子对接技术进一步筛选，得到化合物102个，结果显示这些化合物主要是萜类，分布在见霜黄、慈竹、佩兰等中草药中，这些中草药以菊科药用植物为主，药味以辛、苦为主，药性多寒、温，多归于肝、肺经。选取排名前5的化合物进行作用模式分析，结果显示其与受体XO有较强的亲和作用，有进一步实验验证的价值。结论 在菊科植物及其亲缘关系比较接近的药用植物当中，可能发现潜在的天然XOI化合物，为探索新型XOI先导化合物提供参考。

Virtual Screening of Natural Xanthine Oxidase Inhibitors from Chinese Herbal Medicines

Objective To explore natural xanthine oxidase inhibitors (XOIs) and their distribution by pharmacophore-based virtual screening and literature mining.Methods Potential natural XOIs were screened out from 23 033 natural products of Chinese herbal medicine by pharmacophore-based virtual screening and data mining technologies. The potential compounds with inhibitory activities against xanthine oxidase (XO) were preliminarily screened out by absorption, distribution, metabolism, excretion and pharmacophore. Molecular docking was used to further screen XOIs and the compounds with a high degree were selected for the analysis of the underlying mechanism. Data mining was used to analyze the distribution law of compounds in Chinese herbal medicine.Results The pharmacophore model of XOI was constructed by the HypoGen algorithm. A total of 165 potential active compounds were obtained. Afterward, 102 compounds were further screened out by molecular docking. The results showed that these compounds were represented by terpenoids and mainly distributed in Blumea lacera (Burm.f.) DC., Sinocalamus affinis (Rendle) McClure, and Eupatorium fortunei Turcz. Those Chinese herbal medicines are mostly distributed in the Compositae family, and are pungent and bitter in flavor and cold and warm in nature, acting on the liver and lung meridians. The top 5 compounds were selected for action pattern analysis. The results showed that those compounds had strong affinity with the receptor XO and were potential for further experimental validation.Conclusion Potential natural XOIs may be found in Compositae plants and compositae relative medicinal plants. This study is expected to provide references for the exploration of new XOI lead compounds.