1,8-萘酰亚胺类衍生物的合成及细胞活性研究

Synthesis and Evaluation of the Antiproliferative Activities of 1,8-Naphthalimide Derivatives

以4-溴-1,8萘二甲酸酐作为先导化合物,通过氨解、亲核取代合成了9个1,8-萘酰亚胺类衍生物,通过质谱(MS)、核磁共振氢谱(^(1)H-NMR)、核磁共振碳谱(^(13)C-NMR)表征其结构,采用CCK8法检测目标化合物对乳腺癌MCF-7、肺癌H460、肝癌Hep G2的细胞活性。结果表明,9个衍生物中目标化合物3b的体外抗肿瘤活性较优,对H460最为敏感,作用48 h的半抑制浓度IC_(50)=4.12±0.36μM。1,8-萘酰亚胺类衍生物对癌细胞具有一定的体外生长抑制作用,有望发展为一种新型的抗肿瘤候选化合物,用于癌症的化学预防和治疗。

To design and synthesize 1,8-naphthalimide derivatives and evaluate their cytotoxicity in vitro.1,8-naphthalimide derivatives were synthesized by ammonolysis and nucleophilic substitution reaction with 4-bromo-1,8-naphthalene dicarboxylic anhydride as the lead compound. Their structures were characterized by MS,^(1)H-NMR and^(13)C-NMR. CCK8 assay was used to detect the inhibitory effect of the target compounds in the human cell lines H460, HepG2 and MCF-7 in vitro. A series of 1,8-naphthalimide derivatives with different substituents were successfully synthesized and characterized. Among them, the target compound 3 b has better antitumor activity in vitro and is the most sensitive to H460. The IC_(50)of compound 3 b for 48 h was 4.12±0.36 μM.1,8-naphthalimide derivatives can inhibit the proliferation of cancer cells and may be an emerging new type of anti-tumor candidate compounds for the chemoprophylaxis and treatment of cancer.