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目的:研究合成了一种新型金刚烷类氮氧化物并进一步探讨其体外抗肝癌活性。方法:以金刚烷甲酸和Tempol类氮氧自由基为原料,运用双靶标设计原理,合成目标化合物;MTT法测定目标化合物对人肝癌细胞SMMC7721,HepG2,MHCC-97H,BEL-7404以及L02正常肝细胞株的抑制率;流式细胞仪测定目标化合物对BEL-7404细胞周期和凋亡的影响。结果:利用IR、MS、元素分析对目标化合物结构进行了确证;体外实验显示,与Tempol、5-FU、索拉非尼3个阳性药相比,化合物2对各种肝癌细胞均产生了不同的抑制作用,对BEL-7404细胞抑制作用最好,IC50为(7.8±2.9)μmol·L-1且毒性最小,并通过阻滞细胞周期和诱导凋亡来抑制细胞增殖。结论:本研究合成的目标化合物,有望开发成结构新颖、选择性好、不良反应小的抗肿瘤药物,值得进一步研究。
OBJECTIVE: To study the synthesis of a new type of adamantane nitrogen oxides and to further explore their anti-liver cancer activity in vitro. Methods: The target compounds were synthesized by using the double target design principle using adamantanecarboxylic acid and Tempol nitroxides as the raw materials. The target compounds were determined by MTT method to determine the inhibitory effect of the target compound on human hepatoma cells SMMC7721, HepG2, MHCC-97H, BEL-7404 and L02 normal liver The inhibitory rate of cell lines was determined by flow cytometry. The effects of the target compounds on the cell cycle and apoptosis of BEL-7404 cells were determined by flow cytometry. Results: The structures of target compounds were confirmed by IR, MS and elemental analysis. In vitro experiments showed that Compound 2 had different effects on all kinds of hepatoma cells compared with the three positive drugs Tempol, 5-FU and sorafenib The inhibitory effect on BEL-7404 cells was the best, with the IC50 of (7.8 ± 2.9) μmol·L-1 and the lowest toxicity. Cell proliferation was inhibited by arresting cell cycle and inducing apoptosis. Conclusion: The target compounds synthesized in this study are expected to be developed into new anticancer drugs with novel structure, good selectivity and small adverse reactions, which deserves further study.