含氮芥基查尔酮类衍生物的合成、晶体结构及抗肿瘤活性  

Synthesis,Crystal Strutures and Antitumor Activity of Novel Ni-trogen Mustard-Linked Chalcones

作　　者：方线文[1] 周丽珍[1] 成昭[1] 杨美盼[1] 杨秉勤[1] 

机构地区：[1]西北大学化学与材料科学学院天然产物及功能分子教育部重点实验室,西安710069

出　　处：《有机化学》2013年第3期523-529,共7页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(No.21172178)资助项目~~

摘　　要：根据拼药原理,将氮芥类抗肿瘤药物的药效基团N,N-二(2-氯乙基)氨基拼接到查尔酮结构中,合成出了一系列新型含氮芥基的查尔酮衍生物3a～3r,并用1H NMR,IR,HRMS-ESI及X射线对其结构进行了确证.采用MTT法对所合成的化合物进行了体外抗肿瘤活性测试,结果表明部分化合物对所选肿瘤细胞的增殖有较强的抑制作用,其中,化合物3j和3l对K562的IC50值分别为20.01和18.6μmol/L;对HepG2的IC50值分别为43.46和21.39μmol/L.实验培养并得到了目标产物3e和3l的晶体结构,X射线分析表明化合物3e和3l都属三斜晶系,P-1空间群.A series of novel nitrogen mustard-linked chalcones 3a-3r were synthesized by linking the N,N-bis（2- chloro- ethyl）amine pharmacophore of nitrogen mustards to the chalcone＇s framework. Their structures were characterized by 1H NMR, IR, ESI-HRMS and X-ray techniques. The antitumor activities of the nitrogen mustard-linked chalcones were evaluated against K562 and HepG2 cell lines by an MTT assay. The results reveal that some of the title compounds exhibit potent anti-proliferative activities against selected tumor cells. Among which, compounds 3j against K562 and HepG2 with IC50 values of 20.01 and 43.46μmol/L, and 31 against K562 and HepG2 with IC50 values of 18.6 and 21.39 μmol/L, respectively. Suitable crystals of 3e and 31 were obtained, and the X-ray diffraction analysis indicates that compounds 3b and 3e are both belong to triclinic, slaace ~roun P- 1.

关 键 词：查尔酮 氮芥 合成 晶体结构 抗肿瘤活性 

分 类 号：TQ463[化学工程—制药化工]