去甲氧基姜黄素Mannich碱衍生物的合成及体外抗肿瘤活性研究  

Synthesis and antiproliferative effect of Mannich bases of demethoxycurcumin derivatives

作　　者：刘冰弥[1,2] 张美慧[2] 陶淑娟[2] 夏明钰[3] 董金华[2] 

机构地区：[1]辽宁大学药学院,辽宁沈阳110036 [2]沈阳药科大学基于靶点的药物设计与研究教育部重点实验室,辽宁沈阳110016 [3]沈阳药科大学药学院,辽宁沈阳110016

出　　处：《中国药物化学杂志》2014年第4期271-278,共8页Chinese Journal of Medicinal Chemistry

摘　　要：目的设计并合成去甲氧基姜黄素的曼尼希碱衍生物,评价其体外抗肿瘤增殖活性。方法以乙酰丙酮为起始原料,与香草醛及对羟基苯甲醛经两次Adol缩合制得去甲氧基姜黄素,乙酰化保护后再经亲核取代反应引入双苄基,然后经脱保护及Mannich反应合成目标化合物。采用MTT法测定了目标化合物对人宫颈癌细胞、人乳腺癌细胞、人肝癌细胞、人纤维肉瘤细胞及人慢性髓原白血病细胞等5种细胞的抗增殖活性。结果与结论合成了14个未见文献报道的化合物,其中11个为去甲氧基姜黄素的Mannich碱类化合物,结构经1H-NMR和HR-MS确证;初步药理结果显示活性大多高于去甲氧基姜黄素。Demethoxycurcumin derivatives bearing Mannich base moiety were designed for enhanced stability and improved water-solubility. Eleven demethoxycurcumin derivatives bearing hydrophilic amino moiety were synthesized from acetyl acetone and vanillin, 4-hydroxybenzaldehyde via a total of six step reaction containing Aldol condensation, acetylation protection, alkylation, deprotection and Mannich reaction, and characterized by 1H-NMR and HR-MS spectra. The antiproliferative effect in five human tumor cell lines in vitro were tested by MTI＂ assay. Preliminary pharmacological results showed that most of target compounds were more potent than demethoxycurcumin. The structure-activity relationships revealed that the introduction of sterically small hydrophilic amino group was favorable to the enhancement of antiproferative activity.

关 键 词：去甲氧基姜黄素 去甲氧基姜黄素衍生物 MANNICH碱 抗肿瘤活性 

分 类 号：R914[医药卫生—药物化学]