金雀异黄素衍生物5-羟基-4'-硝基-7-取代氧基异黄酮的合成及抗肿瘤活性研究

目的:寻找新型的以细胞信号转导为靶点抗肿瘤活性物质.方法:根据先导化合物金雀异黄素的结构,设计合成了一类金雀异黄素衍生物:5-羟基-4'-硝基-7-取代氧基异黄酮.以氯苄为起始原料,经取代、硝化、Friedel-Crafts反应和环合,再与各种卤代烃反应;采用MINI法对合成的目标化合物进行了体外抑制MDA-MB-435肿瘤细胞增殖实验.结果:得到2类重要中间体:4'-硝基脱氧安息香和4'-硝基金雀异黄素(4-6)和 6个目标化合物,其中5-羟基-4'-硝基-7-甲氧基异黄酮(4-1)、5-羟基-4'-硝基-7-烯丙氧基异黄酮(4-2)、5-羟基-4'-硝基-7-对氯苄氧基异黄酮(4-3)、5-羟基-4'-硝基-7-苄氧基异黄酮(4-4)和5-羟基-4'-硝基-7-乙氧基异黄酮(4-5)为首次报道.除化合物(4-6)具有较好的抗肿瘤活性外,其余化合物抗肿瘤活性都较弱.结论:在7位羟基上引入简单烃基不能提高该类化合物的抗肿瘤活性.

Synthesis of genistein derivatives:5-hydroxy-4'-nitro-7-substituted-oxo-isoflavone and their antitumor effects

Objective: To search for novel antitumor agents targetin g the cell signal transduction.Methods: According to the structur e of the lead compound: genistein,a genistein derivative,5 hydroxy 4' nitro 7 sustituted oxo isoflavones were designed and synthesized.The antitumor acti vities of the compounds on MDA MB 435 cell line were evaluated using MINI meth od.Results: Two important intermediates: 4' nitrodeoxybenzoin a nd 4' nitrogenistein(4 6) and 6 title compounds were synthesized using benzy l chloride as the starting material.The reaction included substitution,nitration ,Friedel Crafts reaction and cyclation.Five compounds 5 hydroxy 7 methoxyl 4' nitro isoflavone(4 1),7 allyloxy 5 hydroxy 4' nitro isoflavone(4 2),7 (p chlorobenzyloxy) 5 hydroxy 4' nitro isoflavone(4 3),7 benz yloxy 5 hydroxy 4' nitro isoflavone(4 4),7 ethoxyl 5 hydroxy 4' nit ro isoflavone(4 5) were firstly reported.It was showed that compound (4 6) ha d good antitumor activity,and others had weaker antitumor effects.Conclu sion: Introduction of simple alkyls to 7 posion hydroxy cannot enhance the antitumor effects of this type of compounds.