【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。更多还原

【Abstract】 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 MTT 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.更多还原