岭南中药三桠苦生物碱及其抗肿瘤活性研究

Study on Alkaloids and Their Antitumor Activities in Melicope Ptelefolia

目的:研究岭南中药三桠苦生物碱及其抗肿瘤活性成分。方法:利用硅胶柱色谱、Sephadex LH-20、反向柱色谱(ODS),从芸香科植物三桠苦茎中分离、纯化生物碱类成分。通过NMR光谱技术和理化性质鉴定化合物结构。结果:从该植物中分离鉴定出8个生物碱类化合物,分别为吴茱萸春碱、茵芋碱、香草木宁碱、白鲜碱、4-dihydro-3-hydroxy-5-methoxy-2,2-dimethy pyrano(2,3-b)quinoline、R-(+)-platydesmin、4-methoxy-2(1H)-quinolinone、7-羟基白鲜碱。以人肝癌细胞HepG-2、胃癌细胞BGC为研究对象,利用CCK-8法分析8个生物碱的体外抗肿瘤活性并借助分子对接技术探讨其作用机制。结论:4-dihydro-3-hydroxy-5-methoxy-2,2-dimethy pyrano(2,3-b)quinoline、R-(+)-platydesmin对这两种肿瘤细胞均具有较高的抑制活性,通过分子对接技术,发现这两个生物碱与肿瘤细胞的细胞周期蛋白依赖性蛋白激酶(CDK)存在相互作用,初步阐释了其抗肿瘤活性机制。

Objective:To study the alkaloids and antitumor activities of Melicope Ptelefolia.Methods:Using silica gel column chromatography,Sephadex LH-20,ODS to isolate and purify alkaloids from the stem of Melicope Ptelefolia(Champ.ex Benth)Hartley.The structures of the alkaloids were identified by NMR spectroscopy and physicochemical properties.Results:The result showed eight known alkaloids were isolated,Evolitrine,Skimmianine,Kokusaginine,Dictamnine,4-dihydro-3-hydroxy-5-methoxy-2,2-dimethy pyrano(2,3-b)quinoline,R-(+)-platydesmin、4-methoxy-2(1 H)-quinolinone、7-hydroxydictamnine,respectively.In addition,CCK-8 method was used to analyze the antitumor activities of eight alkaloids in vitro,and the mechanism of action were explored by molecular docking technology.Conclusion:The results showed that the IC50 values of 4-dihydro-3-hydroxy-5-methoxy-2,2-dimethyl pyrano(2,3-b)quinoline and R-(+)-platydesmin were 26.4μm and 23.6μm for HepG-2 cells and 21.8μm and 24.2μm for BGC,respectively,which indicated that these two alkaloids have high inhibitory activity on these two kinds of tumor cells.Through molecular docking technology,we found that 4-dihydro-3-hydroxy-5-methoxy-2,2-dimethyl pyrano(2,3-b)quinoline and R-(+)-platydesmin may interact with CDK,which further confirmed the mechanismthe about antitumor activity of these two alkaloids.