2-芳基取代喹唑啉-4(3H)-酮的合成及体外抗肿瘤活性研究  

Synthesis and in vitro antitumor activity of 2-aryl substituted quinazolin-4(3H)-one

作　　者：仝红娟 刘斌[1,2] TONG Hong-juan;LIU Bin(School of Pharmacy,Shaanxi Institute of International Trade&Commerce,Xi’an 712046,China;Collaborative Innovation Center of Green Manufacturing Technology for Traditional Chinese Medicine in Shaanxi Province,Xi’an 712046,China)

机构地区：[1]陕西国际商贸学院医药学院,陕西西安712046 [2]陕西省中药绿色制造技术协同创新中心,陕西西安712046

出　　处：《化学研究与应用》2020年第2期233-238,共6页Chemical Research and Application

基　　金：陕西省自然科学基础研究计划(面上)项目(2019JQ-924,2018JM7046)资助;陕西国际商贸学院“中药药效物质研究”创新团队(SSY18TD01)建设项目资助

摘　　要：以靛红酸酐、醋酸铵和芳香腈为原料,在碘化亚铜的催化下合成得到一系列2-芳基取代喹唑啉-4(3H)-酮(1a^1j),产物结构经1H NMR和ESI-MS表征。并以靛红酸酐和苯腈的反应为模型反应,考察影响产物1a收率的因素,确定最佳反应条件为:醋酸铵为反应溶剂;物料比为n(苯甲腈)∶n(靛红酸酐)=1.1∶1;碘化亚铜的量为n(CuI)∶n(靛红酸酐)=0.10∶1,在120℃反应4 h。在最佳反应条件下,化合物1a收率87%。采用MTT法测定所合成的化合物1a^1j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1h对A549细胞的体外生长具有较明显的抑制作用,IC50为10.2μmol·L^-1,可以作为抗肿瘤药物研究的先导化合物。A series of 2-aryl substituted quinazolin-4(3H)-one derivatives(1a^1j)were synthesized through the reaction of isatoic anhydrous with NH4OAc and aryl nitrile compounds in the presence of cuprous iodide as catalyst,and their structure were confirmed by 1H NMR and ESI-MS.The effect of conditions on the yield of product 1a was investigated as model reaction.The optimal conditions on the yield of compound 1a were as follows:NH4OAc as solvent;the mole ratio of n(benzaldehyde)∶n(isatoic anhydrous)=1.1∶1,the amount of CuI was n(CuI)∶n(isatoic anhydrous)=0.10∶1,the reaction was at 120℃for 4 h.The product of 1a was obtained in 87%yield.The target compounds 1a^1j were tested for their in vitro antitumor activity against human hepatoma carcinoma cell line HepG2 and human non-small lung canner A549 cells by means of colorimetric MTT assay.Among the tested compounds,compound 1h exhibited activity against A549 with IC50 values of 10.2μmol·L^-1.Therefore,compound 1h was worthy to be a lead compound for the design and synthesis of new antitumor agent.

关 键 词：喹唑啉衍生物 喹唑啉酮 喹唑啉-4(3H)-酮 合成 抗肿瘤活性 

分 类 号：O626.4[理学—有机化学]