基于PI3K靶点的芹菜素衍生物设计、合成及分子对接研究  

Design,Synthesis,and Molecular Docking of Apigenin Derivatives Based on PI3K Target

作　　者：何贝桥 高雅婷 梁淼[1] 梁丽娜 张园园[1] 王波[2] HE Beiqiao;GAO Yating;LIANG Miao;LIANG Lina;ZHANG Yuanyuan;WANG Bo(College of Chinese Medicine,Beijing University of Chinese Medicine,Beijing 102400,China;Department of Pharmacy,People′s Hospital of the Ningxia Hui Autonomous Region,Yinchuan 750000,China)

机构地区：[1]北京中医药大学中药学院,北京102400 [2]宁夏回族自治区人民医院药学部,宁夏银川750000

出　　处：《化学与生物工程》2022年第7期47-51,共5页Chemistry & Bioengineering

摘　　要：以芹菜素为母核,设计合成了一系列目标化合物7-O-β-D-芹菜素葡萄糖苷、7-O-β-D-芹菜素半乳糖苷和7-O-β-D-芹菜素阿拉伯糖苷。先将D-葡萄糖、D-半乳糖和D-阿拉伯糖分别依次全乙酰化、溴代,然后采用Koenigs-Knorr法将溴代糖引入芹菜素的7位羟基,脱除糖上的乙酰基,得到目标化合物。利用AutoDock Vina软件分别将目标化合物与PI3Kα、PI3Kβ、PI3Kγ和PI3Kδ蛋白进行分子对接。结果表明,合成的目标化合物与设计一致,结构经1HNMR、13CNMR和ESI-MS表征;目标化合物与PI3K蛋白的亲和力高于芹菜素的。设计合成的3个目标化合物有被进一步开发为PI3K抑制剂的潜力。Taking apigenin as the parent nucleus,we designed and synthesized a series of target compounds,such as 7-O-β-D-apigenin glucoside,7-O-β-D-apigenin galactoside,and 7-O-β-D-apigenin arabinoside.Firstly,D-glucose,D-galactose,and D-arabinose are acetylated and brominated successively.Then,the bromo-polysaccharide is introduced into the 7-hydroxyl group of apigenin by Koenigs-Knorr method,and the acetyl groups on the polysaccharide were removed to obtain the target compounds.Moreover,we carried out molecular docking between the target compounds and PI3Kα,PI3Kβ,PI3Kγ,and PI3Kδproteins by AutoDock Vina.The results show that the synthesized target compounds are consistent with the design compounds,and their structures are characterized by 1HNMR,13CNMR,and ESI-MS.The affinity of the target compound with PI3K protein is higher than that of apigenin.The designed and synthesized target compounds have the potential to be further developed as PI3K inhibitors.

关 键 词：芹菜素 PI3K抑制剂 合成 分子对接 

分 类 号：R914.2[医药卫生—药物化学]