2-取代-4-氨基喹唑啉衍生物的合成及抗肿瘤活性研究  

Synthesis and Antitumor Activity of 2-Substituted-4-Aminoquinazoline Derivatives

作　　者：黄馨怡 余佳 余刚[1,3] 徐广灿 孟雪玲 徐必学[1,3] HUANG Xin-yi;YU Jia;YU Gang;XU Guang-can;MENG Xue-ling;XU Bi-xue(State Key Laboratory of Functions and Applications of Medicinal Plants,Guizhou Medical University,Guiyang 550014,China;School of Pharmaceutical Sciences,Guizhou Medical University,Guiyang 550025,China;The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences,Guiyang 550014,China)

机构地区：[1]贵州医科大学,省部共建药用植物功效与利用国家重点实验室,贵阳550014 [2]贵州医科大学药学院,贵阳550025 [3]贵州省中国科学院天然产物化学重点实验室,贵阳550014

出　　处：《中国药学杂志》2023年第16期1461-1469,共9页Chinese Pharmaceutical Journal

基　　金：贵州省高层次创新型人才培养计划资助(黔科合平台人才[2016]5678);贵州省科技计划项目资助(黔科合基础-ZK[2021]一般070)。

摘　　要：目的寻找高活性、低毒性的新型抗肿瘤药物。方法以(S)-(+)-扁桃酸和2-氨基苯甲酰胺为原料,经过缩合、分子内环化、氧化、氯化、偶联等反应,共设计合成19个2-取代-4-氨基喹唑啉衍生物,经1H-NMR、^(13)C-NMR和^(19)F-NMR进行了结构确证。采用MTT法测定了目标化合物对PC-3、A549、K562、MDA-231和HeLa 5种肿瘤细胞的体外生长抑制活性。结果测试结果显示,部分目标化合物对上述5种肿瘤细胞均有不同程度的生长抑制作用。其中,化合物8a对HeLa细胞、8b和8c对K562细胞具有显著的抑制作用,半数抑制浓度(IC50)分别为3.05、3.31、2.03μmol·L^(-1)。结论本实验合成的目标化合物大多数具有一定的抗肿瘤活性,可为多样化2-取代-4-氨基喹唑啉类抗肿瘤药物的设计合成提供参考依据。OBJECTIVE To find efficient and low toxicity anti-tumor drugs.METHODS A series of novel 2-substituted-4-aminoquinazoline derivatives were designed and synthesized starting from(S)-(+)-mandelic acid and 2-aminobenzamide by condensation,intramolecular cyclization,oxidation,chlorination and coupling reaction.The structures of target compounds were identified by 1H-NMR,13C-NMR and^(19)F-NMR.Their antitumor activities against PC-3,A549,K562,MDA-231 and HeLa cells were evaluated by using MTT assay.RESULTS The results showed that some of the target compounds displayed different degrees of inhibitory effects against the five cancer cells.Among them,8a exhibited significant inhibitory effects against HeLa cells with a IC50 values of 3.05μmol·L^(-1),8b and 8c exhibited significant inhibitory effects against K562 cells with the IC50 values of 3.31μmol·L^(-1)and 2.03μmol·L^(-1)respectively.CONCLUSION Most of the target compounds synthesized show certain anti-tumor activity,which provide a basis for further research on the derivatives of 2-substituted-4-aminoquinazoline.

关 键 词：喹唑啉 抗肿瘤活性 含氟化合物 噻唑蓝法 合成 

分 类 号：R914.5[医药卫生—药物化学]