新颖的2,6-二氯-3,5-二硝基甲苯衍生物的设计,合成及抗肿瘤活性的评价

摘要

本文设计、合成了一系列结构新颖的2,6-二氯-3,5-二硝基甲苯衍生物,并且评价了它们对五种细胞系(A431,HepG2,A549,HT-29和HEK-293)的活性.与顺铂相比,大多数化合物对一种或多种细胞系表现出中等或者显著性的细胞毒性及高选择性.对其构效关系(SARs)初步的研究表明,含有苯基(1-哌嗪基)甲酮基团的化合物,特别是在苯环4位氯原子取代的化合物具有更高的活性.发现化合物4g是最有潜力的衍生物,其对A431,Hep G2,A549,HT-29和HEK-293细胞的IC50分别为1.04,3.20,6.93,4.10和20.15 tmol/L,其活性结果优于在临床上使用最广泛的化疗药物之一的阳性药顺铂.%A series of novel 2,6-dichloro-3,5-dinitrotoluene derivatives were designed,synthesized in the present study,and their antitumor activities against five cell lines (A431,HepG2,A549,HT-29 and HEK-293) were tested.Most of the compounds exhibited moderate-to-significant cytotoxicity and high selectivity against one or more cell lines in comparison with cisplatin.Studies on their preliminary structure-activity relationships (SARs) indicated that compounds containing phenyl (piperazin-1-yl) methanone groups,especially chlorine atom at 4-position of the phenyl ring,were more effective.Compound 4g was found to be the most potent derivative with IC50 values of 1.04,3.20,6.93,4.10 and 20.15 μmol/L against A431,Hep G2,A549,HT-29 and HEK-293 cell lines,respectively,which was better than positive control cisplatin,one of the most clinically used chemotherapeutic drugs.