基于分子对接技术的飞龙掌血抗炎活性生物碱筛选及其作用机制  

Screening of anti-inflammatory alkaloids of Toddalia asiatica and the action mechanism based on molecular docking technology

作　　者：罗才荣 刘杰 梁妍 盛钰 何芋岐 周威 LUO Cairong;LIU Jie;LIANG Yan;SHENG Yu;HE Yuqi;ZHOU Wei(School of Pharmacy,Guizhou Medical University,Guiyang 550025,Guizhou,China;School of Pharmacy,Zunyi Medical University,Zunyi 563099,Guizhou,China)

机构地区：[1]贵州医科大学药学院,贵州贵阳550025 [2]遵义医科大学药学院,贵州遵义563099

出　　处：《贵州医科大学学报》2021年第6期639-646,654,共9页Journal of Guizhou Medical University

基　　金：国家自然科学基金(81360681);贵州省科技支撑项目[黔科合支撑(2021)一般415];贵州省自然科学基金(2020-1Y404);贵州省大学生创新创业项目(S202010660006)。

摘　　要：目的采用分子对接技术探讨飞龙掌血抗炎活性生物碱的筛选及其作用机制。方法采用Lipinski规则初筛检索得到的65个飞龙掌血生物碱化合物组成配体数据库,选择7个与抗炎活性密切相关的IκB激酶β(IKK-β)、丝裂原活化蛋白激酶(MAPK)、肿瘤坏死因子α(TNF-α)、核转录因子κB1(NF-κB1)、诱导型一氧化氮合酶(iNOS)、环氧合酶2(COX-2)及巨噬细胞迁移抑制因子(MIF)组成靶点数据库,并进行可行性验证;采用分子对接软件Lib Dock模块进行分子对接,以DrugBank数据库中对上述靶点具有抑制作用的上市药物作为参考,设置靶点-上市药物和原配体最低得分值为阈值。结果白屈菜红碱等19个化合物符合Lipinski规则,分子对接得到14个得分高于阈值的化合物,其中Demethylnitidine、1,3-二环己基脲、N-反式-阿魏酰酪胺、光叶花椒碱和(7 Z)-N-(4′-methoxyphenethyl)-3-methoxy-4-hydroxycinnamamide具有多靶点效应。结论化合物Demethylnitidine、1,3-二环己基脲、N-反式-阿魏酰酪胺、光叶花椒碱、(7 Z)-N-(4′-methoxyphenethyl)-3-methoxy-4-hydroxycinnamamide、飞龙掌血喹啉、5-甲氧基白藓碱、木兰花碱是飞龙掌血生物碱具有抗炎活性的主要成分,可通过作用于IKK-β、MAPK、MIF及COX-2等相关炎症因子发挥抗炎作用。Objective To investigate the potential anti-inflammatory alkaloids of Toddalia asiatica and their mechanism of action by molecular docking.Methods A ligand database was composed of 65 alkaloids from T.asiatica obtained from preliminary screening using Lipinski rule.Seven proteins[IκB kinaseβ(IKK-β),mitogen-activated protein kinase(MAPK),tumor necrosis factor alpha(TNF-α),nuclear factor kappa beta 1(NF-κB1),induciblenitric oxide synthase(iNOS),cyclooxygenase 2(COX-2)and macrophage migration inhibitory factor(MIF)]were chosen to form a target database and carry out feasibility verification.Molecular docking was performed using the Lib Dock module of molecular docking software,with the approved drugs that had inhibitory effects on the above targets in the DrugBank database as reference,and the lowest value of the target-listed drugs and the original ligand was set as the threshold.Results Nineteen compounds were conformed to Lipinski rule such as chelerythrine,14 compounds with scores higher than the threshold were screened out.Of which,demethylnitidine,dicyclohexylurea,N-cis-feruloyltyramide,nitidine and(7 Z)-N-(4′-methoxyphenethyl)-3-methoxy-4-hydroxycinnnamide had multi-target effect.Conclusion The compounds demethylnitidine,dicyclohexylurea,N-cis-feruloyltyramide,nitidine and(7 Z)-N-(4′-Methoxyphenethyl)-3-Methoxy-4-hydroxycinnnamide,toddaquinoline,5-methoxydictamnine and magnoflorine may be the main component with anti-inflammatory activity of alkaloids from T.asiatica.It is speculated that they may play an anti-inflammatory role by acting on related inflammatory factors such as IKK-β,MAPK,MIF,and COX-2.

关 键 词：生物碱类 飞龙掌血 抗炎 分子对接 虚拟筛选 计算机辅助药物设计 

分 类 号：R285.5[医药卫生—中药学] Q946.88[医药卫生—中医学]