摘要
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- 4 35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
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.
出处
《第二军医大学学报》
CAS
CSCD
北大核心
2004年第1期111-113,共3页
Academic Journal of Second Military Medical University
