2-(3-丁炔酰胺基苯基) 苯并噻唑衍生物的合成及抗肿瘤活性研究

Synthesis and biological evaluation of 2-(3-butynoicamidophenyl) benzothiazole derivatives as antitumor agents

摘要: 以4-氟-3-硝基苯甲酸为起始原料，通过两条合成路线，经5～7步反应得到20个全新的2-（3-丁炔酰胺基苯基）苯并噻唑类化合物。目标化合物的结构经¹H NMR和HR-MS鉴定。采用MTT法考察了其对5种肿瘤细胞株（HCT116、Mia-PaCa2、U87-MG、A549、NCI-H1975）的抗增殖作用，结果表明大部分化合物选择性地对其中的3种肿瘤细胞具有明显的抗增殖活性，其中化合物14c对人脑胶质母细胞瘤U87-MG细胞、化合物14h对结肠癌HCT116细胞的IC₅₀值均在1×10^-8 mol·L^-1数量级水平，在此基础上对该类化合物进行了初步构效分析。

Abstract: A series of 2-(3-butynoicamidophenyl)benzothiazole derivatives were synthesized starting from 4-fluoro-3-nitrobenzoic acid.Structures of all the synthesized compounds were confirmed by ¹H NMR and HR-MS.Their antitumor activities against human tumor cells lines (HCT116, Mia-PaCa2, U87-MG, A549, NCI-H1975) were evaluated by MTT assay.The results revealed that most of the synthesized compounds showed potent activities against HCT116, Mia-PaCa2, U87-MG tumor cells lines.Particularly, compounds 14c and 14h exhibited better activity with IC₅₀ values of 1×10^-8 mol·L^-1 against U87-MG and HCT116 respectively.The structure-activity relationship of compounds was also discussed preliminarily.