6,7-二甲氧基喹啉衍生物的合成及体外抗肿瘤活性研究

Synthesis and in vitro antitumor activity of 6,7-dimethoxyquinoline derivatives

以3,4-二甲氧基苯胺和丙二酸为原料,经过多步反应合成得到一系列6,7-二甲氧基喹啉衍生物(3~7b),中间体及产物结构经1H NMR和ESI-MS表征。并着重考察了Suzuki反应中,物料比对化合物5a和5b收率的影响,确定适宜物料比为n(化合物4)∶n(乙烯基硼酸频哪醇酯)=1∶2.0。在该反应条件下,化合物5a和5b收率分别为54.5%和33.8%。采用MTT法测定6,7-二甲氧基喹啉衍生物3~7b对人肝癌细胞HepG2及人非小细胞肺癌A549的体外抗肿瘤活性。结果表明,化合物7b对HepG2细胞的体外生长具有显著的抑制活性,IC50为8.9±0.95μM·L^(-1)。

A series of 6,7-dimethoxyquinoline derivatives(3~7b)were synthesized from 3,4-dimethoxyaniline and malonic acid by multi-step reaction.The structure of the intermediates and products were characterized by 1H NMR and ESI-MS.The effect of mole ratio on the yields of compounds 5a and 5b in Suzuki reaction was also investigated.The suitable mole ratio was determined as n(compound 4)∶n(vinylboronic acid pinacol cyclic ester)=1∶2.0.The yields of 5a and 5b were 54.5%and 33.8%respectively under this reaction conditions.Subsequently,The antitumor activities of 6,7-dimethoxyquinoline derivatives 3~7b against HepG2 cells and non-small-cell lung carcinoma A549 cells in vitro were determined by MTT assay.The preliminary activity test results showed that compound 7b had significant inhibitory activity on the growth of HepG2 cells in vitro,the IC 50 was 8.9±0.95μM·L^(-1).