苦参碱类TNF-α抑制剂的合成、抗炎活性评价和分子对接研究  

Synthesis of TNF-α inhibitors, anti inflammatory activity evaluation and molecular docking study of matrine derivatives

作　　者：刘旭[1] 梁跃辉[1] 赵晓秋[1] 王松青[1] 蔡捷[2] 张敏[1] 王立升[1] 

机构地区：[1]广西大学化学化工学院新药筛选中心,广西南宁530004 [2]广西医科大学科学实验中心,广西南宁530021

出　　处：《计算机与应用化学》2016年第5期521-524,共4页Computers and Applied Chemistry

基　　金：国家自然科学基金资助项目(21462003);中国博士后科学基金资助项目(2015M572419);广西教育厅重点资助项目(2013ZD003)

摘　　要：肿瘤坏死因子-α(TNF-α)是人体内重要的炎症因子。相关研究证明,TNF-α与苦参碱的抗炎活性密切相关,是苦参碱的抗炎靶标之一。将其作为受体靶标,根据药物拼接原理,以及分子对接的结果,从化合物数据库中筛选出具有酚羟基结构和水杨酸结构的活性基团,以苦参碱为母体拟合出81440个衍生物,其中对接计算得到与TNF-α结合打分值较为优异的衍生物19个,并将其合成。新化合物在小鼠耳廓肿胀和脚趾肿胀的药理实验中均显现出良好的抗炎活性,结果显示其与TNF-α的对接打分和药理实验相似。Tumor necrosis factor-a （TNF-a） is an inflammatory cytokine in human body. It is important in systemic and cutaneous defense, homeostasis, and many disease states. Preliminary studies have also shown that anti-inflammatory activity of matrine is associated with TNF-α. With matrine as precursor, according to the principle of drug registration, 19 novel compounds, which have the phenolic hydroxyl group and the salicylic acid structure, were designed and synthesized. Acute inflammation models of xylene induced the mice auricle swelling and carrageenan induced that the mice toe swelling were used to investigate the anti-inflammation activity of the synthetic matrine derivatives. The results showed that all compounds have good effect. The results of TNF-α docking are consistent with the pharmacological tests.

关 键 词：肿瘤坏死因子(TNF-α) 分子对接 抗炎 苦参碱 药物合成 

分 类 号：R917[医药卫生—药物分析学] R284.1[医药卫生—药学]