水溶性姜黄素前药制备及其体外抗肿瘤实验研究  

Water Soluble Curcumin Prodrug Synthesis and Its Antitumor Activity in Vitro

作　　者：蒋福升[1] 徐秀玲[1] 金波[1] 陈铌铍[1] 高承贤[1] 丁志山[1] 吕圭源[1] 

机构地区：[1]浙江中医药大学,杭州310053

出　　处：《中国药学杂志》2009年第19期1492-1496,共5页Chinese Pharmaceutical Journal

基　　金：浙江省自然科学基金资助项目(Y206776);浙江省中医药重点项目研究计划(2005Z001);浙江省教育厅科研项目(Y200805067)

摘　　要：目的合成聚乙二醇负载的、生物可降解的姜黄素(Cur)前药,以解决Cur水溶性等问题,并增强疗效,为开发新型Cur制剂奠定基础。方法以单甲氧基聚乙二醇为载体,氨基酸为连接臂,合成Cur前药;通过紫外光谱法、核磁共振波谱法对合成产物进行结构鉴定;采用直接观察法对其水中溶解性进行测定;最后通过MTT法对其体外抗肿瘤活性及特点进行分析。结果通过三步法合成了Cur前药,紫外光谱及核磁氢谱确证为预期产物,且合成率较高;水溶性结果表明,产物溶解度大于0.25 mol.L-1,同比游离Cur提高了1.5×105倍以上,增溶显著;体外对人肝癌细胞株HepG2仍具有较强的抑制活性,且抑制率随浓度增高及处理时间延长而增强,前药处理24 h时的IC50为(59.3±2.5)μmol.L-1,而48 h后的IC50为(6.8±1.4)μmol.L-1,表现为"缓释、减毒效果"。结论本实验成功合成了Cur前药,方法简单、合成率高、产物水溶性好,并且能够缓慢释放起到抗肿瘤效果,表现出较好的应用开发前景,值得进一步研究开发。OBJECTIVE To synthesize the polyethylene glycol loaded, biodegradable curcumin prodrug for improving the water solubility and effects of curcumin. METHODS Curcumin prodrug was synthsized by chemical liquid phase synthesis method. UV-Vis spectroscopy and NMR spectroscopy were carried out to verify the products. The water solubility of the final product was measured by direct observation method, its antitumor activity and properly in vitro were analyzed by MTT method. RESULTS Curcumin prodrug was prepared with high yield, and confirmed as the expected products. It showed high water solubility that was more than 0.25 μmol·L^-1 at room temperature, and 1.5× 10^5 times greater than curcumin. MTT results indicated that the prodrug showed great inhibition ratio against HepG2 cell lines, after 24 and 48 h treatment. The IC50 of the prodrug were （59.3±2.5） and （6.8±1.4）μmol·L^-1, respectively. The inhibition of curcumin prodrug on HepG2 cell lines showed concentration and time dependented manner with delayed-release and reducing toxicity property. CONCLUSION It＇s a simple and high-yield synthesis method of the curcumin prodrug. It increased the water solubility of curcumin dramatically. The prodrug showed great antitumor activity by means of delayed-release. The results showed good application and development prospect, deserved further research.

关 键 词：姜黄素 前体药物 聚乙烯二醇类 抗肿瘤药 

分 类 号：R944[医药卫生—药剂学]