5-氟尿嘧啶类衍生物的设计、合成及其抗肿瘤活性研究  

Design, synthesis and anticancer activity of 5-fluorouracil derivatives

作　　者：高丽丽[1] 庞国勋[1] GAO Li-li;PANG Guo-xun(Department of Pharmacy, Hebei General Hospital, Shijiazhuang 05000)

机构地区：[1]河北省人民医院药学部,石家庄050000

出　　处：《中南药学》2018年第4期484-487,共4页Central South Pharmacy

摘　　要：目的合成一系列含5-氟尿嘧啶(5-FU)结构的衍生物并对此类化合物进行抗肿瘤活性研究。方法以5-FU为起始原料,通过加成、缩合,与邻硝基苯氧乙酸类载体通过酯化反应得到目标化合物,并用1H-NMR和MS确证其结构。MTT法检测目标化合物对细胞A549、Hep G 2、He La和正常细胞WI-38的抑制作用。结果目标化合物对肿瘤细胞均有一定的抑制活性,尤其是化合物9对细胞A549的抑制作用[IC50=(3.04±0.48)μmol·L-1]明显优于阳性对照5-FU[IC50=(49.81±1.49)μmol·L-1],且对于正常细胞的毒副作用较小。结论该合成路线所需反应条件温和,便于操作,且目标化合物9具有较好的抗肿瘤活性,值得进一步研究。Objective To synthesize a series of 5-fluorouracil （ 5-FU ） derivatives and to determine their anticancer activity. Methods The target compounds were synthesized via addition reaction, condensation and esterification with 5-FU and phenoxy acetic acid as the main starting materials. The structure of target compounds was validated by 1H-NMR and MS. The inhibitory effects on the cell proliferation of the target compounds were investigated by MTT assay. A549, HepG 2, HeLa and WI-38 cells were chosen for the experiment. Results The title compounds showed certain antitumor activities, and the bioactivity of compound 9 [IC50 = （3.04± 0.48） μmol · L-l] was significantly better than that of the positive control 5-FU [IC50 = （49.81 ± 1.49） μmol ·L-1] with lower toxicity to normal cells WI-38. Conclusion The synthetic path is simple with mild reaction conditions and easy to operate. Compound 9 has shown better anticancer activity, and is worthy of further study.

关 键 词：5-氟尿嘧啶 合成 抗肿瘤活性 

分 类 号：R979.1[医药卫生—药品] R96[医药卫生—药学]