基于分子对接技术的豆科喹喏里西啶类生物碱抑制血管新生的活性成分虚拟筛选  

Virtual screening of anti-angiogenesis quinolizidine alkaloids from Leguminosae plant

作　　者：于雅楠 陈锡欣 刘怡[2] 赵林林 陈磊 王淑美 YU Ya-nan;CHEN Xi-xin;LIU Yi;ZHAO Lin-lin;CHEN Lei;WANG Shu-mei(School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China;School of Chinese Medicine, Southern Medical University, Guangzhou 510515, China;Key Laboratory of Traditional Chinese Medicine Digitalization Quality Evaluation Under State Administration of Traditional Chinese Medicine, Guangzhou 510006, China;Research Center for Traditional Chinese Medicine Quality Engineering Technology Under Guangdong University, Guangzhou 510006, China)

机构地区：[1]广东药科大学中药学院,广东广州510006 [2]南方医科大学中医药学院,广东广州510515 [3]国家中医药管理局中药数字化质量评价技术重点研究室,广东广州510006 [4]广东高校中药质量工程技术研究中心,广东广州510006

出　　处：《中草药》2018年第7期1640-1646,共7页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(81403063;81673556);广东省基础与应用基础研究专项资金(广东省自然科学基金资助)项目(2017A030313753)

摘　　要：目的基于化合物的系统筛选探讨喹喏里西啶类生物碱发挥抗肿瘤等作用的机制。方法应用虚拟筛选技术,收集豆科植物中现已分离鉴定的喹喏里西啶类生物碱103个,选择8个与血管新生密切相关的靶点,应用Discovery Studio 2.5(DS2.5)软件的Lib Dock模块进行分子对接,并以DrugBank中对各靶点确证有抑制作用并已上市的小分子药物为参照,设定各靶点对应的已上市小分子药物最低打分为阈值,初筛出排名前10%的候选化合物,再以原配体打分值为参考开展系统筛选研究。结果最终筛选出打分值高于原配体的候选化合物共计19个,并初步揭示了喹喏里西啶类生物碱抑制血管新生的作用靶点。结论喹喏里西啶类生物碱可能通过抑制血管新生发挥抗肿瘤、抗糖尿病血管并发症等作用。相对于传统筛选,虚拟筛选技术节约了大量时间、精力和物力,为研发血管新生抑制剂类药物提供了一定的参考。Objective To investigate the mechanism of quinacridine alkaloids based on the systematic of screening compounds that play antitumor effect. Methods The virtual screening technique was used and collected 103 quinolizidine alkaloids from Leguminosae plants, and selected eight targets, which were closely related to angiogenesis.The compounds were screened by using the Lib Dock module in Discovery Studio 2.5（DS 2.5） software. In addition, the small-molecule approved drugs of targets from Drug Bank database have scores, the minimum score of each target＇s approved drugs as threshold and the original ligand scoring were set as a reference. Results Nineteen compounds were screened out, which scores were higher than the minimum score of approved drugs as well as being in the top of 10%, and the mechanism of quinolizidine alkaloids anti-angiogenesis was preliminarily revealed. Conclusion The results suggest that the quinolizidine alkaloids may inhibit angiogenesis to play the role of antitumor, diabetic vascular complications and so on. Compared with traditional screening, virtual screening technology saves a lot of time, energy and resources, provided a new method for the development of angiogenesis inhibitor drugs.

关 键 词：喹喏里西啶类生物碱 血管新生 分子对接 虚拟筛选 抗肿瘤 糖尿病血管并发症 

分 类 号：R285.5[医药卫生—中药学]