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

关键词:  人参二醇  生物电子等排体  NO供体  肉桂酸衍物  细胞毒活性

Key words:  Panaxadiol  bioisosterism  No donor  Cinnamic acid derivatives  Cytotoxicity

摘要:

目的 为了获得细胞毒活性更强人参二醇衍生物 方法 利用生物电子等排原理制备3位胺基-人参二醇,再合成人参二醇3位胺基的肉桂酸类、NO供体类衍生物以及其它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核磁共振、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等肿瘤细胞株进行了细胞毒活性评价。结果 药理活性评价结果显示,化合物6c、7以及7j对五株肿瘤细胞均有较强的抑制活性,特别是化合物7对HL-6与SMMC-7721细胞抑制的IC₅₀分别为3.41,4.51 μM,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。

Abstract:

OBJECTIVE In order 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 have not been reported in the literature, and their structures have been confirmed by 1H NMR, 13C 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 IC50 values of compound 7 against HL-6 and SMMC-7721 cells were 3.41 and 4.51 μM, respectively. It is significantly superior to panaxadiol in cytotoxicity. CONCLUSION These results show that 7 and 7j can be used as promising lead compounds for further research.