5-氮杂-5'-脱氧胞嘧啶核苷的合成及其抗肿瘤活性筛选  

Synthesis and antitumor activity of 5-Aza-5'-deoxycytidine

作　　者：林志财[1] 李俊[1] 汤文建[1] 唐敏芳[1] 张义龙[1] 王亚丽[1] 

机构地区：[1]安徽医科大学药学院,合肥230032

出　　处：《安徽医科大学学报》2010年第5期634-637,共4页Acta Universitatis Medicinalis Anhui

基　　金：安徽省科技攻关项目(编号:06013134B);安徽高校省级自然科学研究项目(编号:KJ2008B171)

摘　　要：目的合成并分离5-氮杂-5'-脱氧胞嘧啶核苷(5-aza-5'dC)的α,β异构体,并研究其抗肿瘤活性。方法以氰基胍为原料合成并分离5-aza-5'dC的α,β异构体,用不同浓度的5-aza-5'dC作用于肝癌细胞株BEL-7402,胃癌细胞株SCG-7901,MTT法观察细胞生长曲线,流式细胞仪检测细胞周期分布情况。结果通过1H-NMR、13C-NMR和HR-MS确认5-aza-5'dC的α,β异构体的结构,药理活性实验表明β异构体能够显著抑制肿瘤细胞的生长,α异构体作用较弱;流式细胞检测表明经过5-aza-5'dC作用后,肝癌细胞株BEL-7402呈现G0/G1期和G2/M期双期阻滞,胃癌细胞株SCG-7901呈现G2/M期阻滞。结论 5-aza-5'dC的合成方法简单易行,其β异构体对BEL-7402、SCG-7901肿瘤细胞具有抑制增殖和细胞周期阻滞作用。Objective To synthesize and separate the α and β isomers of 5-Aza-5＇-deoxycytidine（ 5-aza-5＇dC） , and explore the antitumor activity of 5-aza-5＇dC. Methods We synthesized the 5-aza-5＇dC with the cyanoguanidine as raw material. The carcinoma cell lines were treated with different concentrations of 5-aza-5dC. Then MTT assay was used to detect the growth curves of cells. Flow cytometry was adopted to discover cell cycle distribution. Results The structures of the α and β isomers of 5-aza-5＇dC were confirmed by spectral analysis including 1H-NMR,13CNMR and HR-MS. Proliferation of the hepatoma carcinoma cell BEL-7402 and gastric carcinoma cell SCG-7901 were both inhibited by the β isomer 5-aza-5＇dC treatment,and the α isomer was inferior. The hepatoma carcinoma cell BEL-7402 were blocked in G0 /G1 phase and G2 /M phase,while the cells SCG-7901 were blocked in G2 /M phase. Conclusion This readily manipulated process can synthesize a bioactive compound β isomer 5-aza-5＇dC. To the hepatoma carcinoma cell line BEL-7402 and the gastric carcinoma cell line SCG-7901,β isomer 5-aza-5＇dC can inhibit the proliferation and block cell cycle.

关 键 词：增殖细胞/药物作用 细胞周期/药物作用 

分 类 号：R979.1[医药卫生—药品]