依曲替酸衍生物的合成及抗肿瘤活性研究  

Synthesis and antitumor activity of acitretin derivatives

作　　者：王璐[1] 陈飞虎[1] 石静波[1] 洪凡青[1] 徐佼[1] 汪渊[2] 

机构地区：[1]安徽医科大学药学院,合肥230032 [2]安徽医科大学分子生物学中心实验室和生物化学教研室、安徽省基因研究重点实验室,合肥230032

出　　处：《安徽医科大学学报》2010年第5期638-642,共5页Acta Universitatis Medicinalis Anhui

基　　金：安徽省自然科学基金资助项目(编号:050430705)

摘　　要：目的合成依曲替酸酯及酰胺衍生物,以寻找新的具有抗肿瘤活性的药物。方法以依曲替酸和三氟甲苯衍生物为原料,合成一系列依曲替酸酯及酰胺衍生物。在体外通过四甲基偶氮唑蓝(MTT)试验法检测其对急性早幼粒细胞白血病细胞株NB4生长抑制的作用;利用流式细胞术检测细胞周期的变化情况。结果制备出依曲替酸酯及酰胺衍生物并通过1H-NMR、13C-NMR和HR-MS确认结构。MTT结果显示部分化合物对NB4细胞增殖的抑制作用较为明显;细胞周期分析显示G0/G1期细胞增加,而S期减少。结论初步的药理实验结果显示将依曲替酸通过酯键和酰胺键与三氟甲苯衍生物连接起来能增强其对NB4细胞的诱导分化作用。Objective To synthesis a series of acitretin derivatives and search new medicine for carcinoma. Methods New compounds were designed and synthesized which connect acitretin and trifluorophenyl derivatives, through eater or amide bond by condensation reaction. The profileration of NB4 cells was measured by MTT method. Flow cytometry were used to observe the alteration of proliferation,differentiation characteristics,and cell cycle. Results Twelve new compounds were prepared and their structures were confirmed by spectral analysis concluding 1 H-NMR,13 C-NMR and MS. Some of the compounds showed more growth inhibition activities. The proportion of cells in G0 /G1 phase increased while the cells in S phase decreased. Conclusion According to the anti-tumor activity consequence between acitretin and its derivatives,some of the new compounds can induce NB4 cell lines differentiation efficiently.

关 键 词：维甲酸/类似物和衍生物/药理学 白血病 肿瘤/药物疗法 细胞分化/药物作用 

分 类 号：R986[医药卫生—药品] R329.21[医药卫生—药学]