4-(4-羟基-3-甲氧基苯甲基)姜黄素合成及其抗肿瘤活性  

Study on the synthesis and antitumor activity of 4-(4-hydroxy-3-methoxybenzyl)curcumin

作　　者：刘洋[1] 陈纯[2] 李娜[3] 许建华[2] 

机构地区：[1]福建医科大学药学院药物化学系,福建福州350004 [2]福建医科大学药学院药理学系,福建福州350004 [3]福建医科大学附属协和医院药剂科,福建福州350001

出　　处：《中国医院药学杂志》2011年第14期1156-1159,共4页Chinese Journal of Hospital Pharmacy

基　　金：国家自然科学基金(编号:30873101);福建省科技重点项目(编号:2009Y0025);福建省教育厅项目(编号:JA10150)

摘　　要：目的:合成4-(4-羟基-3-甲氧基苯甲基)姜黄素(C086),并对其体内外抗肿瘤活性进行评价。方法:以芳香醛、乙酰丙酮为原料,Knovenagel缩合、氢化还原、Claisen-Schmidt缩合三步反应制备目标化合物。以姜黄素为对照,MTT法考察目标化合物对人慢性粒细胞白血病急变细胞株K562、人急性髓系白血病细胞株HL-60、人肝肿瘤细胞株HepG2、小鼠黑色素瘤细胞株B-16、人结肠癌细胞株SW480、人神经母细胞瘤细胞株SH-SY5Y、人胰腺癌细胞株Bxpc-3、人胃癌细胞株MGC80-3的抑制活性。考察目标化合物体内抑制人结肠癌SW480裸鼠移植性肿瘤活性。结果:目标化合物结构经核磁和质谱确证,对上述细胞株的IC50值依次为2.90,4.11,4.11,3.55,4.78,7.92,18.8,17.1μmol.L-1,均明显比姜黄素强,100mg.kg-1.d-1灌胃给药对人结肠癌SW480裸鼠移植性肿瘤的抑瘤率为40.7%,小鼠的体质量无明显减轻。结论:合成了4-(4-羟基-3-甲氧基苯甲基)姜黄素,体外对多种肿瘤细胞抑制活性明显强于Cur,体内能明显抑制结肠癌移植瘤的生长。OBJECTIVE To synthesize 4-（4-hydroxy 3 methoxybenzyl）eurcumin（C（）86） and to test its antitumor activity. METHODS 4-（4-hydroxy-3-methoxybenzyl）curcumin was synthesized from vanillin and aeetylacetone by Knovenagel conden sation,hydrogenation and Claisen-Schmidt condensation. The antiproliferative activities in vitro were tested with eight cancer cell lines including K562, HL60, HepG2, Bl6, SW480, SH SY5Y, Bxpc-3 and MGC80 3 by MTT assay. Curcumin was used for comparative purpose. C086 was tested for in vivo inhibition of human colon cancer sw480 tumor growth of nude mice. RESULTS The structure of C086 was confirmed by ^1H NMR, ^13C-NMR and MS. The ICs. of 4-（4-hydroxy 3 methoxy benzyl）cureumin on K562, HL-60, HepG2, B16, SW480, SH SY5Y, Bxpc-3 and MGC80 3 were 2. 91）, 4. 11,4. 11,3.55, 4. 78,7. 92,18. 8 and 17. 1 μmol·L^-1 respectively. These data showed that 086 was more active than curcumin. Compound C086 100 mg·kg^-1·d^-1 was able to inhibit the growth of sw480 xenograft in nude mice by 40. 7G. The weight of the mice had no sig nificant decrease. CONCLUSION 4-（4-hydroxy-3-methoxybenzyl） eurcumin was synthesized for the first time. C086 showed significant antiproliferative activity on tumor over eurcumin in vitro and was able to inhibit the growth of colon cancer xeuograft in nude mice in vivo.

关 键 词：姜黄素 姜黄素类似物 抗肿瘤活性 

分 类 号：R96[医药卫生—药理学]