摘要/Abstract

以4-溴-1,8-萘酐为原料, 经亲核取代反应合成了系列手性氨基醇修饰的萘酰亚胺衍生物NI1~NI8. 四甲基偶氮唑蓝(MTT)法研究了其细胞毒性, 发现含有伯羟基氨基醇修饰的萘酰亚胺衍生物中R型的细胞毒性好于S型异构体. 经紫外光谱、荧光光谱和激光共聚焦实验研究了化合物(R)-2-(2-(二甲基氨基)乙基)-6-((1-羟基-2-丙烷基)氨基)-萘酰亚胺(NI1)和(S)-2-(2-(二甲基氨基)乙基)-6-((1-羟基-2-丙烷基)氨基)-萘酰亚胺(NI2)与DNA分子和HeLa细胞的相互作用, 发现其能有效与脱氧核糖核酸(DNA)络合, 键合常数达到10⁴ L?mol^–1; 且NI1和NI2与HeLa细胞作用可定位于细胞核. 流式细胞实验结果显示NI1和NI2能够使细胞周期阻滞于S期而抑制细胞增殖. 小鼠体内血液毒性结果显示NI1对血液中的红细胞、白细胞和血小板无明显影响.
关键词: 萘酰亚胺, 细胞核, 手性, 细胞周期
A series of novel chiral amino alcohol modified naphthalimide derivatives NI1~NI8 were designed and synthesized by nucleophilic substitution reaction. Furthermore, their cytotoxicities were studied by thiazolyl blue tetrazolium bromide (MTT) method. The cytotoxicity of the R-type isomer in the naphthalimide derivatives with primary hydroxyl amino alcohol modification was better than that of the S-type isomer. In addition, deoxyribonucleic acid (DNA) binding interactions and fluorescence imaging of (R)-2-(2-(dimethylamino)ethyl)-6-((1-hydroxypropan-2-yl)amino)-naphthalimide (NI1) and (S)-2-(2-(dimethylamino)ethyl)-6-((1-hydroxypropan-2-yl)amino)-naphthalimid (NI2) with Ct-DNA and HeLa cells were investigated. NI1 and NI2 showed strong binding interactions with Ct-DNA with a bonding constant of 10⁴ L/mol. And NI1 and NI2 exhibited nucleus-targeting imaging for HeLa cells. NI1 and NI2 mainly arrested the S phase. Moreover, the hematoxic results of NI1in mice showed no significant effects on the red blood cells, white blood cells and platelets in the blood.
Key words: naphthalimide, nucleus, chiral, cell cycle


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