合成一系列喹啉类衍生物,初步筛选出候选药物TW9183,并对其体外抗肿瘤活性进行研究.4,7-二氯喹啉通过亲核取代、酰氯化及缩合反应得到TW9183.采用四甲基偶氮唑盐法(MTT)、平板克隆、划痕法、HOECHST 33342染色、蛋白免疫印迹及流式细胞术研究TW9183对3种人类肿瘤细胞(HElA,A549,SMMC-7721)的体外抑制作用.产物结构经红外光谱、核磁共振氢谱、碳谱、电喷雾质谱和元素分析表征确证.实验结果表明:TW9183能有效抑制3种肿瘤细胞的增殖,但对正常人脐静脉内皮细胞(HuVEC)无影响;HOECHST染色可见肿瘤细胞凋亡明显;TW9183能促进CASPASE-3活化形式的表达;划痕实验中肿瘤细胞迁移能力显著下降;流式细胞术表明其能将3种肿瘤细胞阻滞于g2/M期.In this paper,a series of quinoline derivatives were synthesized.A lead compound,TW9183,was screened out preliminarily and investigated the anti-tumor activities in vitro.By nucleophilic substitution,acylchloride and condensation reaction,TW9183 could form from 4,7-dichloro quinoline.MTT plate cloning,scratching assay,Hoechst 33342 staining,western blot and flow cytometry were utilized to test the inhibitory effects of TW9183 against three types of human tumor cells(Hela,A549,and SMMC-7721)in vitro.The structure of the product was characterized by IR,1 H NMR,13 C NMR,ESI-MS and elemental analysis.The results of assay showed that TW9183 could inhibit the proliferation of three types of tumor cells effectively,but have no effect on HUVEC;Hoechst 33342 staining revealed the obvious apoptosis of tumor cells;TW9183could promote the expression of caspase-3activation form;scratching assay suggested that the migration ability of tumor cells decreased dramatically;and flow cytometry detection demonstrated that cell cycle of tumor cells were arrested in the G2/M phase after treated with TW9183.福建省泉州市科技计划重点项目(2013Z35
