新型苦参碱衍生物的设计合成及其体外抗炎活性  

Synthesis of novel matrine derivatives and their in vitro anti-inflammatory activity

作　　者：郭俊香[1] 梁萌[1] 张春梅[1] 王亮[1,2] 胡宏岗[1] 

机构地区：[1]第二军医大学药学院有机化学教研室,上海200433 [2]烟台大学药学院药物化学教研室,烟台264005

出　　处：《第二军医大学学报》2011年第11期1223-1226,共4页Academic Journal of Second Military Medical University

基　　金：国家自然科学基金(20902109)~~

摘　　要：目的设计合成新型苦参碱衍生物,并研究其体外抗炎活性。方法以槐果碱为起始原料,经硫代和经典的Michael加成反应得到10个目标化合物;所得化合物均考察了其体外对抗炎因子TNF-α释放以及NF-κB转染的影响。结果合成的目标化合物经1 HNMR和ESI-MS确证其结构。所得化合物体外对TNF-α的释放和NF-κB转染均具有一定的抑制作用,其中化合物1f对TNF-α的释放抑制作用最强,IC50为9.4μmol/L。结论苦参碱的13位引入小的直链氨基侧链能够增强其抗炎活性。Objective To design and synthesize a series of novel matrine derivatives and to investigate their in vitro anti-inflammation activities.Methods Ten novel matrine analogues were synthesized via thiosulfate reaction and classical Michael addition using sophocarpine as the starting material.The effects of all the analogues on TNF-α production and NF-κB transcriptional activity were evaluated in vitro.Results The synthesized compounds were confirmed correct by 1HNMR and ESI-MS.Biological studies showed that the synthetic derivatives had inhibitory effects against TNF-α production and NF-κB transcriptional activity.Compound 1f had the strongest inhibitory effect against TNF-α production,with an IC50 value of 9.4 μmol/L.Conclusion Introduction of liner small substitutes at the 13-position of matrine can enhance its anti-inflammatory activity.

关 键 词：苦参碱 衍生物 肿瘤坏死因子Α NF-ΚB 

分 类 号：R971.1[医药卫生—药品]