穿心莲内酯酰胺类衍生物的合成及其COX-2表达抑制活性

Synthesis of amide derivatives of andrographolide and their inhibitory activities on COX-2 expression

目的:合成穿心莲内酯酰胺类衍生物并研究其对环氧化酶-2(COX-2)表达的抑制活性。方法:根据穿心莲内酯类似物具有与穿心莲内酯相似的生物活性及生物电子等排原理,以穿心莲内酯的3种类似物为原料,在无水甲醇中,经氯化氢气体醇解、酰胺化生成目标化合物。按蛋白质印迹免疫分析法(Western blot)测试此类衍生物对脂多糖诱导的小鼠巨噬细胞中COX-2的表达抑制活性。结果与结论:合成了未见文献报道的12个穿心莲内酯酰胺类衍生物,目标化合物结构经IR,1HNMR,MS与元素分析确证。部分化合物进行了药理活性测试,其中1个目标化合物、2个中间体与穿心莲内酯的抑制活性相当。

Aim：To synthesis the amide derivatives of andrographolide and to study their effects on lipopolysacchride induced COX-2 expression in mouse macrophages. Methods： NaBH4-NiC12 reduction, hydrolysis and amidation were used in the synthesis of the target compounds. The inhibitory activity of COX-2 expression was measured by using Western blot analysis. Results and Conclusion： 14 compounds of amides were semi-synthesized from andrographolide. All the target compounds have been identified by IR, ^1H NMR, MS and elemental analysis. Among these derivatives, one compound and two intermediates showed similar inhibitory potency to that of andrographolide.