摘要
设计合成了9个白藜芦醇酰胺衍生物,并对其抗炎活性进行评价。所得化合物利用^(1)H NMR、^(13)C NMR和ESI-MS等手段进行了结构表征;通过Griess法检测化合物对LPS诱导RAW264.7细胞释放炎症介质NO的抑制活性;荧光法检测化合物对COX-2酶的抑制活性;计算机模拟分子对接探索化合物与COX-2酶的相互作用模式。结果显示,化合物2、7和8对LPS诱导RAW264.7细胞释放NO具有明显抑制作用,同时表现较强的COX-2酶抑制活性。其中,化合物8活性最强,其对COX-2酶的半数抑制浓度IC_(50)值为0.09μmol/L,是白藜芦醇(IC_(50)0.98μmol/L)活性的10倍,具有进一步深入研究的价值。计算机模拟分子对接结果显示,化合物8可通过B环对位羟基与COX-2酶的关键氨基酸残基Tyr385形成氢键相互作用。
In this work, 9 resveratrol amide derivatives are designed, synthesized and evaluated for anti-inflammatory activities. All compounds are characterized by ^1H NMR,^(13)C NMR and ESI-MS spectra. The inhibition of NO production in LPS-induced RAW 264.7 cells of all compounds is tested by Griess method, the COX-2 inhibitory activity of active conpounds is evaluated by fluorescence detection, and the interaction mode between active compounds and COX-2 enzyme is explored through molecular docking. The results indicate that compounds 2, 7 and 8 have significant inhibitory activity on the release of NO from LPS-induced RAW 264.7 cells and exhibit strong COX-2 enzyme inhibitory activity. Specially, compound 8 shows the strongest activity, and its inhibitory activity of COX-2(IC_(50)0.09 μmol/L) is 10 times as strong as that of reveratrol(IC_(50) 0.98 μmol/L), similar to that of the positive control, which is worthy of in-depth study. Molecular docking studies reveal that the para-hydroxyl group of the B ring in compound 8 is hanged with stable hydrogen bond with the key residue Tyr385 of COX-2 enzyme.
作者
辛敏
王璐琼
牟晓凤
赵烽
XIN Min;WANG Lu-qiong;MOU Xiao-feng;ZHAO Feng(School of Pharmacy,Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shan-dong,Key Laboratory of Molecular Pharmacology and Drug Evaluation,Ministry of Education,Y antai University,Yantai 264005,China)
出处
《烟台大学学报（自然科学与工程版）》
CAS
2022年第3期308-315,共8页
Journal of Yantai University(Natural Science and Engineering Edition)
基金
山东省自然科学基金资助项目(ZR2019ZD24)
烟台大学研究生科技创新基金资助项目(YDYB2123)。
关键词
白藜芦醇
合成
酰胺类衍生物
抗炎活性
分子对接
resveratrol
synthesis
amide derivatives
anti-inflammatory activity
molecular docking
