4-烷氧甲酰基苯并(口恶)唑酮类化合物的合成及其体外抗炎活性研究

目的 设计并合成4-烷氧甲酰基苯并唑酮类化合物,并对其进行体外抗炎活性研究.方法 以3-羟基-2-氨基苯甲酸为起始原料,经过酯化、成环和取代反应合成目标化合物,并对其进行结构确证.采用LPS诱导的小鼠巨噬细胞RAW264.7炎症模型,通过Griess法测定细胞培养液中NO的释放量,ELISA法测定细胞培养液中IL-6和IL-1β 的量以评价化合物的体外抗炎活性.结果 共合成了10个目标化合物,均通过ESI-MS、1H-NMR及13C-NMR对其结构进行确证.体外抗炎活性测定结果表明,化合物3d在25μmol/L时对IL-1β 的抑制率达63.96%,对IL-6的抑制率达60.99%,与阳性对照药塞来昔布活性相当.结论 4-烷氧甲酰基苯并唑酮类化合物可通过抑制NO、IL-6和IL-1β 炎症因子的释放而发挥抗炎活性.

Synthesis of 4-alkyloxycarbonyl-benzoxazolone compounds and their anti-inflammatory activities in vitro

Objective To design and synthesize 4-alkyloxycarbonyl-benzoxazolone compounds, and to study their anti-inflammatory activity in vitro. Methods 3-Hydroxy-2-amino benzoic acid was used as the starting material to gain a series of target compounds through esterification, cyclization, and substitution reaction, and their structures were confirmed. Subsequently, all of the synthesized compounds were incubated with lipopolysaccharide (LPS) induced rat macrophage RAW264.7 cell, then the expression of NO, IL-1β, and IL-6 were determined by Griess and ELISA assays kits to evaluate the anti-inflammatory activity in vitro. Results Ten benzoxazolone compounds were synthesized, and the structures were characterized by ESI-MS, 1H-NMR, and 13C-NMR. The anti-inflammatory activity assays showed that compound 3d had good inhibitory activity against IL-1β and IL-6 with inhibition rate of 63.96% and 60.99%, and it was near to that of the control drug celecoxib. Conclusion 4-Alkyloxycarbonyl-benzoxazolone compounds exhibit anti-inflammatory activity by inhibiting the expression of NO, IL-6 and IL-1β.