通过网络药理学和分子对接方法探讨桑白皮治疗2型糖尿病的作用机制。运用中药系统药理学数据库与分析平台筛选桑白皮的活性成分及相应作用靶点,借助DrugBank、GeneCards和TTD数据库检索疾病靶点。活性成分靶点与疾病靶点取交集得到桑白...通过网络药理学和分子对接方法探讨桑白皮治疗2型糖尿病的作用机制。运用中药系统药理学数据库与分析平台筛选桑白皮的活性成分及相应作用靶点,借助DrugBank、GeneCards和TTD数据库检索疾病靶点。活性成分靶点与疾病靶点取交集得到桑白皮作用于2型糖尿病的预测靶点,构建活性成分-潜在靶点网络图和关键靶点蛋白质-蛋白质相互作用(protein protein interaction,PPI)网络。将交集基因进行基因本体(gene ontology,GO)分析和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)富集分析;最后应用AutoDock软件进行活性成分及关键靶点之间的分子对接验证。预测得到桑白皮活性成分25个,桑白皮与疾病的交集靶点126个。PPI网络发现AKT1、IL-6、TNF、VEGFA、TP53、CASP3等可能是桑白皮治疗2型糖尿病的关键靶点。GO富集分析涉及细胞因子信号转导通路、对脂质的反应和凋亡信号通路等生物过程。KEGG通路分析涉及糖尿病并发症中AGE-RAGE信号通路、IL-17信号通路、TNF信号通路、PI3K-Akt等信号通路。分子对接结果显示桑白皮主要成分槲皮素、山奈酚、β-谷甾醇、鸢尾甲黄素B和光果甘草酮与AKT1、IL-6、VEGFA、CASP3均具有较好的结合活性,其中槲皮素与AKT1结合能最低,光果甘草酮与IL-6、VEGFA、CASP3的结合能最低。本研究初步探究了桑白皮治疗2型糖尿病的活性成分、潜在靶点及生物学过程和信号通路,为其临床应用提供了科学依据。展开更多
Two novel N-acyl-3-phenylpyrazol benzophenones were designed and synthesized via cyclization and acylation with 1,3-diphenylpropane-1,3-dione and dimethylformamide dimethylacetal as the starting materials.Both of the ...Two novel N-acyl-3-phenylpyrazol benzophenones were designed and synthesized via cyclization and acylation with 1,3-diphenylpropane-1,3-dione and dimethylformamide dimethylacetal as the starting materials.Both of the newly synthesized compounds were characterized with IR,~1H NMR,^（13）C NMR,HRMS and single-crystal X-ray diffraction.3-Phenyl-1-o-methylbenzoyl-pyrazole-4-benzophenone（5 a） and 3-phenyl-1-p-fuorobenzoyl-pyrazole-4-benzophenone（5 b） crystallize in triclinic system,space group P1.The existence of p-π conjunction effect resulted in correlative bond length shorter than the typical bond length in both of the crystals.The presence of van der Waals forces leads to the stability of the compounds.展开更多
文摘通过网络药理学和分子对接方法探讨桑白皮治疗2型糖尿病的作用机制。运用中药系统药理学数据库与分析平台筛选桑白皮的活性成分及相应作用靶点,借助DrugBank、GeneCards和TTD数据库检索疾病靶点。活性成分靶点与疾病靶点取交集得到桑白皮作用于2型糖尿病的预测靶点,构建活性成分-潜在靶点网络图和关键靶点蛋白质-蛋白质相互作用(protein protein interaction,PPI)网络。将交集基因进行基因本体(gene ontology,GO)分析和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)富集分析;最后应用AutoDock软件进行活性成分及关键靶点之间的分子对接验证。预测得到桑白皮活性成分25个,桑白皮与疾病的交集靶点126个。PPI网络发现AKT1、IL-6、TNF、VEGFA、TP53、CASP3等可能是桑白皮治疗2型糖尿病的关键靶点。GO富集分析涉及细胞因子信号转导通路、对脂质的反应和凋亡信号通路等生物过程。KEGG通路分析涉及糖尿病并发症中AGE-RAGE信号通路、IL-17信号通路、TNF信号通路、PI3K-Akt等信号通路。分子对接结果显示桑白皮主要成分槲皮素、山奈酚、β-谷甾醇、鸢尾甲黄素B和光果甘草酮与AKT1、IL-6、VEGFA、CASP3均具有较好的结合活性,其中槲皮素与AKT1结合能最低,光果甘草酮与IL-6、VEGFA、CASP3的结合能最低。本研究初步探究了桑白皮治疗2型糖尿病的活性成分、潜在靶点及生物学过程和信号通路,为其临床应用提供了科学依据。
基金supported by the National Natural Science Foundation of China(31772208)Heilongjiang Province Postdoctoral Science Foundation(LBH-Z16033)
文摘Two novel N-acyl-3-phenylpyrazol benzophenones were designed and synthesized via cyclization and acylation with 1,3-diphenylpropane-1,3-dione and dimethylformamide dimethylacetal as the starting materials.Both of the newly synthesized compounds were characterized with IR,~1H NMR,^（13）C NMR,HRMS and single-crystal X-ray diffraction.3-Phenyl-1-o-methylbenzoyl-pyrazole-4-benzophenone（5 a） and 3-phenyl-1-p-fuorobenzoyl-pyrazole-4-benzophenone（5 b） crystallize in triclinic system,space group P1.The existence of p-π conjunction effect resulted in correlative bond length shorter than the typical bond length in both of the crystals.The presence of van der Waals forces leads to the stability of the compounds.
