4(3H)-喹唑啉酮衍生物的合成及体外抗肿瘤活性  

Synthesis and in vitro antitumor activity of 4(3H)-quinazolinone derivatives bearing dithiocarbamate chains

作　　者：曹胜利[1] 蒋宇扬[2] 冯玉萍[3] 刘世英[2] 高红核[1] 张玫[1] 万荣[3] 

机构地区：[1]首都师范大学化学系,北京100037 [2]清华大学深圳研究生院 [3]清华大学化学系

出　　处：《药学学报》2007年第7期741-746,共6页Acta Pharmaceutica Sinica

基　　金：北京市自然科学基金资助项目(7042006);北京市教委科技发展项目(KM200710028008)

摘　　要：将6-溴甲基-2-甲基-4(3H)-喹唑啉酮在无水磷酸钾存在下与二硫化碳以及不同的胺反应,合成了一系列具有二硫代氨基甲酸酯侧链的4(3H)-喹唑啉酮衍生物,其结构经ESI-MS,1HNMR,元素分析或HRMS所证实。采用MTT法测定了目标化合物8a^8q对人慢性髓性白血病K562细胞和人宫颈癌Hela细胞的体外抗肿瘤活性,结果表明化合物8q对K562和Hela细胞的体外生长具有显著的抑制作用,IC50值分别为0.5和12.0μmol.L-1,因而可作为抗肿瘤药物研究的先导化合物。A series of 4 （3H） -quinazolinone derivatives bearing dithiocarbamate side chains have been synthesized through the reaction of 6-bromomethyl-2-methyl-4 （3H）-quinazolinone with CS2 and various amines in the presence of anhydrous K3PO4, and their structures were confirmed with ESI-MS, ^1H NMR, elemental analysis or HRMS. The target compounds 8a -8q were tested for their in vitro antitumor activity against human myelogenous leukaemia K562 and human Hela cell lines by means of colorimetric MTT assay. Among the tested compounds, 8q exhibited in vitro inhibitory activity against K562 and Hela cells with IC50 values of 0.5 and 12.0 μmol · L^-1 , respectively. Therefore, compound 8q is worthy to be a lead compound for the design and synthesis of new antitumor agents.

关 键 词：4(3H)-喹唑啉酮 二硫代氨基甲酸酯 抗肿瘤活性 

分 类 号：R916.2[医药卫生—药学]