中文摘要：

目的：对吖啶酰胺基硫脲类衍生物进行体外抗肿瘤活性筛选,并初步探讨其抗肿瘤机制。方法：采用CCK-8法检测该吖啶类化合物4a对人肺癌A549细胞、人鼻咽癌CNE-2细胞、人胰腺癌panc-1细胞、人脑神经母细胞瘤SN-K细胞及人子宫颈癌Hela细胞的体外抗肿瘤活性,并以作用活性最强的细胞进行后续实验;采用HE染色观察药物作用后细胞形态的变化;采用流式细胞术检测药物对肿瘤细胞凋亡和细胞周期影响。结果：吖啶类化合物4a对各肿瘤细胞均显示了一定的抑制作用,对A549、CNE-2、panc-1、SN-K及Hela细胞的IC50分别为（3.59±0.49）mg/L、（17.93±0.02）mg/L、（53.88±0.87）mg/L、（32.34±0.18）mg/L、（37.43±0.12）mg/L,对A549细胞的抑制活性最强。HE染色结果显示吖啶类化合物4a作用A549细胞后,细胞间隙增大,体积变小,核固缩。流式细胞仪检测不同浓度吖啶类化合物4aA549作用48h后,低剂量组、中剂量组、高剂量组的坏死率分别为（2.63±0.21）%、（2.70±1.19）%、（38.80±0.10）%;细胞周期中G2期和S期逐渐增加（P〈0.05）。结论：吖啶类化合物4a对多种肿瘤细胞均有一定的抑制作用,对A549细胞抑制活性最强,其初步作用机制可能是通过将细胞阻滞于G2期和S期,促进细胞凋亡,从而抑制肿瘤细胞生长。

英文摘要：

Objective：To study the antitumor activity of an amidothiourea acridine derivative（ID：4a,patent No.201410521970.6）in vitro,and explore its antitumor mechanism.Methods：The acridine compound 4a and cisplatin（positive control）were diluted at various concentrations and their antitumor activities were tested by CCK-8method with five different human tumor cell lines,including CNE-2,A549,panc-1,SNK and Hela cell lines.HE staining was performed to identify the morphologic change of cancer cells.Flow cytometry was used to detect cell apoptosis and cell cycle.Results：The result of CCK-8detection suggested that the acridine compound 4ahas inhibitory effect on the proliferation of CNE-2,panc-1,SN-K,A549 and Hela.The IC50 value of the acridine compound 4aon different cell lines were 3.59±0.49mg/L,17.93±0.02mg/L,53.88±0.87mg/L,32.34±0.18mg/L and 37.43±0.12mg/L,respectively.A549 cells are the most sensitive cell line in response to acridine compound 4atreatment.Therefore,A549 cell line was chosen for further study.Flow cytometry analysis suggested that acridine compound 4ainduced apoptosis and G2 arrest in a dose-dependent manner.Conclusion：Acridine amidothiourea derivative 4acould significantly inhibit the proliferation of A549 cells in vitro.Acridine amidothiourea derivative 4a-induced G2 cell cycle arrest and apoptosis may be the underlying mechanism responsible for its inhibitory effect on cancer cell lines.