苯并呋喃酮类衍生物的合成及抗肿瘤活性评价  

Synthesis and antitumor activity evaluation of benzofuranone derivatives

作　　者：蔡娟 周剑 董张超 潘博文 石洋 CAI Juan;ZHOU Jian;DONG Zhang-chao;PAN Bo-wen;SHI Yang(School of Pharmacy,Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China;School of Chemistry and Molecular Engineering,East China Normal University,Putuo,Shanghai 200062,China)

机构地区：[1]贵州中医药大学药学院,贵州贵阳550025 [2]华东师范大学化学与分子工程学院,上海普陀200062

出　　处：《化学研究与应用》2024年第7期1577-1585,共9页Chemical Research and Application

基　　金：教育厅青年科技人才成长项目(黔教合KY字[2022]253号)资助;贵州省教育厅高校科技创新团队项目(黔教技[2023]069号)资助。

摘　　要：以苯并呋喃酮和不同取代的苯甲醛为底物,通过羟醛缩合反应,合成了21个苯并呋喃酮类衍生物3a~3u,收率40~91%,用^(1)H-NMR进行结构表征。采用Schrodingers Maestro软件将它们与9个抗肿瘤相关的蛋白进行分子对接预测活性,结果导入Discovery Studio软件进行可视化分析确定结合模式,预测结果表明苯并呋喃酮类衍生物主要通过Pi-Alkyl键、Alkyl键、氢键、范德华力等作用力与靶蛋白结合而发挥作用。进一步对预测活性好的化合物采用MTT法评价抗肿瘤活性,结果发现化合物3h、3g、3u和3n对Hela或A549的活性优于阳性对照药顺铂,IC_(50)分别为8.24±0.54、8.64±0.62、14.22±1.12和15.32±1.06μM。Twenty-one benzofuranone derivatives 3a~3u were synthesized via hydroxyl aldehyde condensation reaction using benzo-furanone and various substituted benzaldehydes as substrates,with yields ranging from 40%to 91%.Their structures were characterized using^(1)H-NMR spectroscopy.Schrodinger's Maestro software was employed to dock these compounds with nine anti-tumor-relat-ed proteins for activity prediction.The results were further analyzed using Discovery Studio software for visual confirmation of the binding modes.The predictions indicated that benzofuranone derivatives primarily exerted their antitumor activity through interactions such as Pi-Alkyl bonds,alkyl bonds,hydrogen bonds,and van der Wals forces with the target proteins.MTT assay was con-ducted to evaluate the antitumor activity of compounds with promising predicted activity,revealing that compounds 3h,3g,3u,and 3n exhibited superior activity against Hela or A549 compared to the positive control cisplatin,with IC_(50) values of 8.24±0.54,8.64±0.62,14.22±1.12,and 15.32±1.06μM,respectively.

关 键 词：羟醛缩合反应 苯并呋喃酮衍生物 抗肿瘤活性 分子对接 结合模式 

分 类 号：O626.1[理学—有机化学]