2-芳基-4-三氟甲基喹唑啉衍生物的合成及抗肿瘤活性研究  

Synthesis and Antitumor Activity of 2-Aryl-4-Trifluoromethylquinazoline Derivatives

作　　者：陈明秀 程莎 代兴 孟雪玲 徐广灿 徐必学[1,3] Chen Mingxiu;Cheng Sha;Dai Xing;Meng Xueling;Xu Guangcan;Xu Bixue(State Key Laboratory of Functions and Applications of Medicinal Plants,Guizhou Medical University,Guiyang,550014;School of Pharmaceutical Sciences,Guizhou Medical University,Guiyang,550025;The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences,Guiyang,550014)

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：《化学通报》2023年第5期598-606,597,513,共11页Chemistry

基　　金：贵州省高层次创新型人才培养计划项目(黔科合平台人才[2016]5678);贵州省科技计划项目(黔科合基础-ZK[2021]一般070,黔科中引地[2022]4015)资助。

摘　　要：为寻找高效低毒的含三氟甲基取代的喹唑啉类新型抗肿瘤活性化合物,以2-硝基-5-氯苯甲酸为原料,通过水解、还原、偶联、环合、三氟甲基加成消除等反应,合成了14个2-芳基-4-三氟甲基喹唑啉衍生物,并通过^(1)H NMR、^(13)C NMR、^(19)F NMR等进行了结构确证。采用MTT法评价了目标化合物对PC3(前列腺癌细胞)、LNCaP(前列腺癌细胞)、K562(人慢性髓系白血病细胞)、HeLa(宫颈癌细胞)和A549(人肺癌细胞)等肿瘤细胞株的生长抑制活性。结果显示,在5μmol/L浓度下,部分目标化合物对上述5种肿瘤细胞均具有较好的生长抑制活性,其中,化合物8c、13e对LNCaP细胞的IC_(50)(半数抑制浓度)分别为2.9和1.9μmol/L,值得进一步深入研究。To find anti-tumor quinazoline compounds with high efficiency and low toxicity,a series of novel 2-aryl-4-trifluoromethylquinazoline derivatives were synthesized starting from 5-chloro-2-nitrobenzoic acid by hydrolysis,reduction,coupling,cyclization,trifluoromethyl addition,and elimination reactions.The structures of target compounds were characterized by^(1)H NMR,^(13)C NMR and^(19)F NMR.Their antitumor activities in vitro against five human cancer cell lines(PC3,LNCaP,K562,HeLa and A549)were demonstrated by MTT assay.The results indicated that some target compounds show inhibitory effect on five human cancer cell lines at 5μmol·L^(-1).Among them,compounds 8c and 13e showed better activities against LNCaP antiproliferative with IC_(50)values of 2.9μmol·L^(-1)and 1.9μmol·L^(-1),respectively.In this study,a rapid synthesis method for the preparation of novel 2-aryl-4-trifluoromethylquinazoline derivatives has been developed,and some of these compounds exhibited certain inhibitory activity.The results of this study will provide a basis for further research on the derivatives of 2-aryl-4-trifluoromethylquinazoline.

关 键 词：喹唑啉 三氟甲基 抗肿瘤活性 MTT法 

分 类 号：TQ460.1[化学工程—制药化工] O626.323[理学—有机化学]