【摘要】 将二氢杨梅素和喹诺酮抗肿瘤化合物的结构特征拼合,设计了一系列3-羟基-4-喹诺酮类化合物;以3,5-二甲氧基苯胺为原料,经还原氨化、弗克酰基化、微波促进闭环、BBr3催化脱甲基、Mannich反应等步骤制备得到16个目标化合物;采用MTT法测定了化合物对肺肿瘤细胞株A549和NCI-H 460的增殖抑制活性。所合成的16个化合物均未见文献报道,其结构经IR、MS、1H NMR确证;活性测试结果显示,多个化合物对两种细胞株均表现出中等的抗增殖活性,化合物11b对NCI-H 46细胞的抑制作用最强。初步构效关系表明:在3-羟基-4-喹诺酮结构的N-1位进入异戊烯基能显著地提高化合物的抗肿瘤活性。更多还原

【Abstract】 A combination of the structural features of dihydromyricetin and quinolone antineoplastic compounds gave rise to 3-hydroxy-4-quinolone motif.Starting from 3,5-dimethoxyaniline,the target compounds were prepared through a reaction cascade,including reductive amination,Friedel-Crafts reaction,microwave assisted ring closure,BBr3catalyzed demethylation and Mannich reaction.Sixteen novel compounds were synthesized,and their structures were confirmed by IR,MS and1H NMR.The antiproliferative activities of the compounds against A549and NCI-H 460 cells were tested in MTT assay.Several compounds exhibited moderate antiproliferative activities against both cell lines,of which,compound 11b displayed the most robust inhibition towards NCI-H 460.Preliminary structural-activity relationships indicated that introduction of isopentenyl into the N-1 position of 3-hydroxy-4-quinolone motif would significantly improve the potency of the compounds.更多还原