以齐墩果酸为先导化合物,设计并合成了6个新型齐墩果酸硫脲类衍生物,化合物的结构经1H NMR确认.利用计算机辅助药物设计方法,对目标化合物与VEGFR-2蛋白的作用模式进行研究,结果表明目标化合物与VEGFR-2蛋白的结合能(评分数值的绝对值)...以齐墩果酸为先导化合物,设计并合成了6个新型齐墩果酸硫脲类衍生物,化合物的结构经1H NMR确认.利用计算机辅助药物设计方法,对目标化合物与VEGFR-2蛋白的作用模式进行研究,结果表明目标化合物与VEGFR-2蛋白的结合能(评分数值的绝对值)均高于母体化合物齐墩果酸,其中化合物Ⅰ5的结合能最高(-554.73 k J/mol).展开更多
目的:基于体外实验和分子对接研究枫杨抑菌活性及机制。方法:以枫杨果、树皮、叶为研究对象,分别研究其水提物和醇提物(70%乙醇)对金黄色葡萄球菌、大肠杆菌、绿脓杆菌、伤寒沙门菌、化脓性链球菌、表皮葡萄球菌的抑菌活性,确定抑菌谱...目的:基于体外实验和分子对接研究枫杨抑菌活性及机制。方法:以枫杨果、树皮、叶为研究对象,分别研究其水提物和醇提物(70%乙醇)对金黄色葡萄球菌、大肠杆菌、绿脓杆菌、伤寒沙门菌、化脓性链球菌、表皮葡萄球菌的抑菌活性,确定抑菌谱和最小抑菌浓度(MIC)。利用活性追踪方法,通过硅胶吸附色谱、薄层色谱等手段,分离单体化合物,并进行抑菌活性研究,选择PBP5、FabI、FabH、FtsZ4个抑菌关键蛋白靶点,利用Systems Dock Web Site软件进行分子对接,研究其抑菌机制。结果:实验发现枫杨果的醇提物抑菌效果最好,对伤寒沙门菌最小抑菌浓度为7.81 mg/mL,首次从枫杨果中分离得到β-谷甾醇、β-胡萝卜苷、齐敦果酸,三个化合物对于PBP5、FabH、FtsZ蛋白靶点Docking score均大于7,结果活性很好。结论:枫杨果醇提物抑菌谱广、抑菌能力强,其可能是通过抑制革兰氏阳性菌细胞壁肽聚糖的合成,以及细菌脂肪酸的生物合成,干扰其生物膜的形成从而抑制细菌的生长和繁殖,从而起到广谱的抗菌效果。展开更多
Inhibiting pancreatic Lipase(PL)and cholesterol esterase(CEase)can effectively control blood triglycerides and cholesterol levels.The interaction characteristics of pentacyclic triterpenoid acids(oleanolic acid[OA],ur...Inhibiting pancreatic Lipase(PL)and cholesterol esterase(CEase)can effectively control blood triglycerides and cholesterol levels.The interaction characteristics of pentacyclic triterpenoid acids(oleanolic acid[OA],ursolic acid[UA],and corosolic acid[CA])with PL and CEase were studied by inhibition kinetics,multispectroscopy,and molecular docking methods.Enzyme inhibition and inhibition kinetics showed that pentacyclic triterpenoid acids effectively inhibited PL and CEase in a competitive manner with IC50 values ranging from 0.077 mg/mL to 0.446 mg/mL.UV-Vis,fourier transform infrared,fluorescence quenching,and circular dichroism analysis demonstrated that OA,UA,and CA disrupted the conformation of PL and CEase through hydrogen bonding and hydrophobic forces,resulting in loose protein structures.Molecular docking analysis revealed that pentacyclic triterpenoid acids could stably bind at key residues in the active site of PL and CEase.Molecular dynamics(MD)simulation further confirmed the stable binding of pentacyclic triterpene acids to PL and CEase.This study suggested that OA,UA,and CA could have an essential value as digestive enzyme inhibitors.展开更多
文摘以齐墩果酸为先导化合物,设计并合成了6个新型齐墩果酸硫脲类衍生物,化合物的结构经1H NMR确认.利用计算机辅助药物设计方法,对目标化合物与VEGFR-2蛋白的作用模式进行研究,结果表明目标化合物与VEGFR-2蛋白的结合能(评分数值的绝对值)均高于母体化合物齐墩果酸,其中化合物Ⅰ5的结合能最高(-554.73 k J/mol).
文摘目的:基于体外实验和分子对接研究枫杨抑菌活性及机制。方法:以枫杨果、树皮、叶为研究对象,分别研究其水提物和醇提物(70%乙醇)对金黄色葡萄球菌、大肠杆菌、绿脓杆菌、伤寒沙门菌、化脓性链球菌、表皮葡萄球菌的抑菌活性,确定抑菌谱和最小抑菌浓度(MIC)。利用活性追踪方法,通过硅胶吸附色谱、薄层色谱等手段,分离单体化合物,并进行抑菌活性研究,选择PBP5、FabI、FabH、FtsZ4个抑菌关键蛋白靶点,利用Systems Dock Web Site软件进行分子对接,研究其抑菌机制。结果:实验发现枫杨果的醇提物抑菌效果最好,对伤寒沙门菌最小抑菌浓度为7.81 mg/mL,首次从枫杨果中分离得到β-谷甾醇、β-胡萝卜苷、齐敦果酸,三个化合物对于PBP5、FabH、FtsZ蛋白靶点Docking score均大于7,结果活性很好。结论:枫杨果醇提物抑菌谱广、抑菌能力强,其可能是通过抑制革兰氏阳性菌细胞壁肽聚糖的合成,以及细菌脂肪酸的生物合成,干扰其生物膜的形成从而抑制细菌的生长和繁殖,从而起到广谱的抗菌效果。
基金support from the National Key R&D Program of China(2019YFD1002404).
文摘Inhibiting pancreatic Lipase(PL)and cholesterol esterase(CEase)can effectively control blood triglycerides and cholesterol levels.The interaction characteristics of pentacyclic triterpenoid acids(oleanolic acid[OA],ursolic acid[UA],and corosolic acid[CA])with PL and CEase were studied by inhibition kinetics,multispectroscopy,and molecular docking methods.Enzyme inhibition and inhibition kinetics showed that pentacyclic triterpenoid acids effectively inhibited PL and CEase in a competitive manner with IC50 values ranging from 0.077 mg/mL to 0.446 mg/mL.UV-Vis,fourier transform infrared,fluorescence quenching,and circular dichroism analysis demonstrated that OA,UA,and CA disrupted the conformation of PL and CEase through hydrogen bonding and hydrophobic forces,resulting in loose protein structures.Molecular docking analysis revealed that pentacyclic triterpenoid acids could stably bind at key residues in the active site of PL and CEase.Molecular dynamics(MD)simulation further confirmed the stable binding of pentacyclic triterpene acids to PL and CEase.This study suggested that OA,UA,and CA could have an essential value as digestive enzyme inhibitors.