人参二醇衍生物的合成及其细胞毒活性研究  

Synthesis and Cytotoxicity Evaluation of Panaxadiol Derivatives

作　　者：蒲洪 董成梅 邹澄 赵庆 段文越 陈艳梅 张莲卿 胡建林 PU Hong;DONG Chengmei;ZOU Cheng;ZHAO Qing;DUAN Wenyue;CHEN Yanmei;ZHANG Lianqing;HU Jianlin(School of Pharmaceutical Sciences,Hunan University of Medicine,Hunan Provincial Key Laboratory for Synthetic Biology of Traditional Chinese Medicine,Huaihua 418000,China;School of Pharmaceutical Sciences,Kunming Medical University,Yunnan Key Laboratory of Pharmacology for Natural Products,Kunming 650500,China;School of Pharmaceutical Sciences,Kunming Health Vocational College,Kunming 650600,China;School of Traditional Chinese Medicine,Yunnan University of Traditional Chinese Medicine,Kunming 650500,China)

机构地区：[1]湖南医药学院药学院,中药合成生物学研究湖南省重点实验室,湖南怀化418000 [2]昆明医科大学药学院,云南省天然药物药理重点实验室,昆明650500 [3]昆明卫生职业学院药学院,昆明650600 [4]云南中医药大学中药学院,昆明650500

出　　处：《中国现代应用药学》2024年第13期1765-1774,共10页Chinese Journal of Modern Applied Pharmacy

基　　金：湖南省自然科学基金项目(2022JJ50294);湖南省教育厅科学研究项目(22B1036);湖南医药学院博士科研启动基金项目(202203)。

摘　　要：目的 制备细胞毒活性更强的人参二醇衍生物。方法 利用生物电子等排原理制备3位氨基-人参二醇,再合成人参二醇3位氨基的肉桂酸类、NO供体类衍生物以及其他类型的人参二醇衍生物18个,其中有12个化合物未见文献报道,其结构均经过^(1)H-NMR、^(13)C-NMR、质谱确证。这些化合物中的16个化合物用MTS法对人白血病细胞株HL-60、肝癌细胞株SMMC-7721、肺癌细胞株A-549、乳腺癌细胞株MCF-7、结肠癌细胞株SW480等肿瘤细胞株进行细胞毒活性评价。结果 药理活性评价结果显示,化合物6c、7以及7j对5株肿瘤细胞均有较强的抑制活性,特别是化合物7对HL-60与SMMC-7721细胞抑制的IC_(50)值分别为3.41、4.51μmol·L^(-1),显著优于人参二醇的细胞毒活性。结论 7和7j可以作为先导化合物进行更深入的研究。OBJECTIVE To obtain stronger cytotoxic activity of panaxadiol derivatives.METHODS The 3-amino panaxadiol was prepared by the bioelectronic isosteric principle,and then 18 derivatives of cinnamic acid,NO donor and other types of panaxadiol derivatives were synthesized,among them,12 compounds had not been reported in the literature,and their structures had been confirmed by ^(1)H-NMR,^(13)C-NMR and mass spectrometry.These compounds were evaluated for their cytotoxic activity by MTS assay against human leukemia cell line HL-60,liver cancer cell line SMMC-7721,lung cancer cell line A-549,breast cancer cell line MCF-7,and colon cancer cell line SW480.RESULTS These results showed that compounds 6c,7 as well as 7j exhibited potent inhibitory activities against all five tumor cells,especially the IC_(50) values of compound 7 against HL-60 and SMMC-7721cells were 3.41 and 4.51μmol·L^(−1),respectively.It was significantly superior to panaxadiol in cytotoxicity.CONCLUSION These results show that 7 and 7j can be used as promising lead compounds for further research.

关 键 词：人参二醇 生物电子等排体 NO供体 肉桂酸衍生物 细胞毒活性 

分 类 号：R284.3[医药卫生—中药学] R965.1[医药卫生—中医学]