具有抗白血病活性的曼尼希碱  

A serial of Mannich bases with anti-leukemia activity

作　　者：冯计周 刘红萍[1] 范莉[1] 黄敏[1] 杨大成[1] 

机构地区：[1]西南大学化学化工学院,重庆市高校应用化学重点实验室,生物有机与药物化学研究所,重庆400715

出　　处：《药学学报》2017年第5期766-772,共7页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(21542003)

摘　　要：为寻找抗白血病活性化合物,本研究以对甲基苯乙酮、芳香醛和芳香胺为原料,借助Mannich反应一锅法合成了33个曼尼希碱,其结构经1H NMR、IR、MS确证;体外活性测试结果表明,在1×10^(-4) mol·L^(-1)浓度下,所有化合物对P338肿瘤细胞生长显示抑制作用,在测试浓度为1×10^(-8) mol·L^(-1)时,化合物TM33抑制活性最好,其抑制率依然高达60.3%、半数抑制浓度IC_(50)低至0.45 nmol·L^(-1)。本研究为新型抗白血病药物的研发提供了新的分子类型。Thirty-three compounds were designed and synthesized directly from three-component, one-pot condensation of 1-（4-methylphenyl）ethanone and aromatic amines with some aromatic aldehydes. The chemical structures of the Mannich bases were confirmed by 1H NMR, IR and MS. The screening results of bioactivity indicated that all of these title compounds possessed the inhibitory activity at the concentration of 1 × 10^-4 mol.L^-1 Among them, the compound TM33 displayed the strongest bioaetivity with the inhibition percentage of 60.3% against P338 cancer cell line at the concentration of 1 × 10^-8 mol.L^-1, and the value of the half maximal inhibitory concentration （IC50） was as low as 0.45 nmol.L^- 1. This study suggests a new type of potential anti-leukemia molecules.

关 键 词：白血病 MANNICH碱 对甲苯乙酮 芳香醛 芳香胺 

分 类 号：R916[医药卫生—药学]