(5-氟脲嘧啶-1-乙酸)-4'-姜黄素酯的合成及抗肿瘤活性  

Synthesis and anti-tumor effect of(5-fluorouracil-1-acetic acid)-4′-curcuminate

作　　者：吴敏[1] 刘洋[1,2] 魏晓霞[1] 郭晓丹[1] 黄秀旺[1,2] 邓艳平[1,2] 许建华[1,2] 

机构地区：[1]福建医科大学药学院,福州350004 [2]福建医科大学临床药理所,福州350004

出　　处：《中国新药杂志》2011年第17期1711-1714,1677,共5页Chinese Journal of New Drugs

基　　金：福建省科技重点项目(2009Y0025);福建省产业技术开发项目(闽发改高技[2008]264号)

摘　　要：目的:合成(5-氟脲嘧啶-1-乙酸)-4'-姜黄素酯并考察其抗肿瘤活性。方法:5-氟脲嘧啶(5-FU)与氯乙酸在碱性条件下反应得到5-氟脲嘧啶-1-基乙酸(3),再与姜黄素成酯得到(5-氟脲嘧啶-1-乙酸)-4'-姜黄素酯(4);MTT法测定化合物4抗HL60、K562、SGC7901、SW480细胞增殖的活性;H22荷瘤小鼠连续腹腔注射给药8 d后颈椎脱臼处死,剥离肿瘤称重,计算抑瘤率。结果:(5-氟脲嘧啶-1-乙酸)-4'-姜黄素酯抑制HL60、K562、SGC7901、SW480细胞增殖的IC50分别为5.774,11.05,17.83,13.67μg.mL-1;经腹腔注射给予不同剂量的化合物4(80,160,320 mg.kg-1),其对H22荷瘤小鼠肿瘤生长的抑制率分别为26.85%,30.65%和61.37%,与阴性对照组比较,320 mg.kg-1剂量组具有显著性差异(P<0.01)。结论:(5-氟脲嘧啶-1-乙酸)-4'-姜黄素酯体外能明显抑制HL60、K562、SGC7901、SW480等肿瘤细胞增殖,对H22荷瘤小鼠肿瘤生长具有抑制作用,并呈一定量效关系。Objective： To synthesize （5-fluorouracil-l-acetic acid）-4＇-curcuminate and investigate its anti-tumor effect. Methods： 5-Fluorouracil （5-FU） reacted to chloroacetic acid in the alkaline environment to prepare 5-fluorouracil-1-acetic acid （3） , then compound 3 was esterified by reacting to cureumin to prepare （5-fluoroura-cil-1-acetic acid）-4＇-curcuminate （4）. Cell proliferation was assayed by MTT method to explore the cytotoxic effect of compound 4 on HL60, K562, SGC7901 and SW480 cells in vitro. The tumor model in mice was established by inoculation of H22 cells. At 8 days after intraperitoneal injection of compound 4, mice were killed, and the subcutaneous sarcoma were isolated and weighted. Results： The IC50 of （5-fluorouracil-l-acetic acid）-4＇-curcuminate calculated by the inhibition rates were 5. 774, 11.05, 17.83 and 13.67 μg·mL^-1 in HL60, K562, SGC7901 and SW480 ceils, respectively. Compound 4 at doses of 80, 160, 320 mg· kg-1 significantly inhibited tumor growth by 26.85% , 30.65% and 61.37% , respectively, as compared with control group. Conclusion： （5-Fluorouracil-1- acetic acid）-4＇-curcuminate synthesized in this study shows an obvious anti-tumor effect in vivo and in vitro.

关 键 词：姜黄素 5氟脲嘧啶 衍生物 抗肿瘤活性 

分 类 号：R979.1[医药卫生—药品]