首页|一种苯并氮杂卓类化合物的合成及抗炎活性研究

一种苯并氮杂卓类化合物的合成及抗炎活性研究

Synthesis and Anti-Inflammatory Activity of a Benzo[b]azepine Compound

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目的:本研究旨在通过电化学方法合成一种新型硒化的苯并氮杂环化合物,1-((4-(叔丁基)苯基)磺酰基)-5-苯基-3-((苯基硒基)甲基)-2,3-二氢-1H-苯并[b]氮杂平,并初步探讨其潜在的抗炎活性及其作用机制.方法:采用电化学方法成功合成了目标化合物,并以CCK-8 法评估了其对小鼠单核巨噬细胞RAW 264.7 的细胞毒性.通过使用脂多糖(LPS)诱导的体外细胞炎症模型,使用不同浓度的化合物进行干预.利用Griess法测定了细胞上清液中的NO含量,ELISA法测定了TNF-α和IL-6 的水平,运用实时荧光定量PCR技术检测TNF-α、IL-1β和IL-6 mRNA表达的情况.结果:以 55%的产率通过电化学方法合成了目标化合物.在 1~100 μmol/L,该化合物对RAW 264.7 细胞无明显毒性.化合物对NO的生成具有显著的抑制效果,其半抑制浓度(IC50)为 0.41 μmol/L,抑制作用呈剂量依赖.在 0.5~2.0 μmol/L的给药浓度下,高剂量组显著降低了RAW 264.7细胞中TNF-α、IL-1β和IL-6的mRNA水平,与LPS诱导的模型组相比差异显著(p<0.01).结论:电化学是一种绿色高效的合成苯并氮卓类化合物的方法.1-((4-(叔丁基)苯基)磺酰基)-5-苯基-3-((苯基硒基)甲基)-2,3-二氢-1H-苯并[b]氮杂平通过抑制RAW 264.7 细胞释放TNF-α、IL-1β和IL-6 等炎性因子,并可能通过调节NO释放的抗炎途径来发挥其抗炎效果,证实了其具有作为抗炎药物的潜力.
Objective:This study aims to synthesize a novel selenium-containing benzo[b]azepine derivative,1-((4-(tert-butyl)phenyl)sulfonyl)-5-phenyl-3-((phenylselanyl)methyl)-2,3-dihydro-1H-benzo[b]azepine,using an electrochemical method,and to preliminarily investigate its potential anti-inflammatory activity and mechanism of action.Methods:We successfully synthesize the target compound by using electrochemical methods and evaluated its cytotoxicity on mouse monocyte/macrophage cell line RAW 264.7 using the CCK-8 assay.An in vitro cellular inflammation model induced by lipopolysaccharide(LPS)is utilized to intervene with different concentrations of the compound.The Griess method is employed to measure the NO content in the cell supernatant,and the levels of TNF-α and IL-6 are determined by ELISA.Additionally,real-time fluorescence quantitative PCR technology is used to detect the expression of TNF-α,IL-1β,and IL-6 mRNA.Results:The target compound is synthesized with a 55%yield through electrochemical methods.Within the concentration range of 1 to 100 μmol/L,the compound shows no significant toxicity to RAW 264.7 cells.The compound exhibited a significant inhibitory effect on NO production,with a half-maximal inhibitory concentration(IC50)of 0.41 μmol/L,and this inhibitory effect is dose-dependent.At the administered concentrations of 0.5 to 2.0 μmol/L,the high-dose group significantly reduced the expression of TNF-α,IL-1β,and IL-6 mRNA in RAW 264.7 cells,with a significant difference compared to the LPS-induced control group(p<0.01).Conclusion:Electrochemical synthesis is a green and efficient method for the synthesis of benzo[b]azepine derivatives.1-((4-(tert-butyl)phenyl)sulfonyl)-5-phenyl-3-((phenylselanyl)methyl)-2,3-dihydro-1H-benzo[b]azepine demonstrates its potential as an anti-inflammatory agent by inhibiting the release of inflammatory factors such as TNF-α,IL-1β,and IL-6 from RAW 264.7 cells,and may exert its anti-inflammatory effects by regulating the NO pathway,thereby confirming its potential as a promising anti-inflammatory drug candidate.

electrochemicalbenzodiazepinegreen synthesisanti-inflammatory activity

胡零、冯育林

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江西中医药大学 中药固体制剂制造技术国家工程研究中心,江西南昌 330006

电化学 苯并氮杂卓 绿色合成 抗炎活性

江西省自然科学基金

20224BAB216115

2024

生物化工

生物化工

ISSN:
年,卷(期):2024.10(3)
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