邻苯二甲酰亚胺-咪唑盐杂合物的合成及生物活性研究

Synthesis and biological activities of phthalimide-imidazolium salt derivatives

以N-溴甲基邻苯二甲酰亚胺为原料,分别与3种咪唑及其衍生物反应,再与溴代烷烃反应合成了18个新型的邻苯二甲酰亚胺-咪唑盐杂合物,并对所合成的新化合物进行了镇痛活性和抗肿瘤活性研究.研究结果表明,化合物11和17均表现出较好的镇痛活性,化合物20表现出较好的抗肿瘤细胞毒活性,对5种肿瘤细胞的活性均高于阳性对照DDP,其中对HL-60细胞株的IC50值为1.86μmol/L,对SMMC-7721、A-549和MCF-7细胞株的抗肿瘤活性分别为DDP的2.5倍、1.9倍和1.8倍.

Commercial N-bromomethyl phthalimide was chosen as the starting material to react with imidaz-ole or its derivatives.Then, 18 phthalimide-imidazolium salts were prepared with the corresponding alkyl bro-mides.They were evaluated in vitro against a panel of human tumor cell lines and analgesic activity.The resultssuggest that compounds 11 and 17 showed good analgesic activity, and compound 20 was found to be the most po-tent derivative against five tumor cell lines investigated and more active than DDP.Compound 20 exhibited cyto-toxic activity selectively against HL-60 cell lines with IC50 value of 1.86 μmol/L and against SMMC-7721 ,A549and MCF-7 cell lines with IC50 2.5-fold, 1.9-fold and 1.8-fold lower than DDP.