3-羟基-4-喹诺酮类化合物的设计、合成及其抗增殖活性

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。

Design, synthesis and antiproliferative activity of 3-hydroxy-4-quinolone compounds

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, BBr₃ catalyzed demethylation and Mannich reaction. Sixteen novel compounds were synthesized, and their structures were confirmed by IR, MS and ¹H NMR. The antiproliferative activities of the compounds against A549 and 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.