摘要
目的以天然提取的丹参素钠为起始原料,设计合成系列新型丹参素酯类衍生物,并初步研究其抗心肌缺血活性。方法采用传统药物设计方法,将丹参素与不同醇反应合成丹参素酯类衍生物。通过体外缺氧诱导H9c2大鼠心肌细胞损伤模型,初步评价新衍生物的生物活性,分析其构效关系。结果合成了16种丹参素酯类衍生物,经1H NMR和MS确证结构;药理结果显示部分衍生物在设定的作用浓度范围内,表现出强于丹参素的抗心肌缺血活性。结论在保持邻二酚羟基的前提下,将羧酸基团酯化修饰能明显改善化合物的药理活性。
OBJECTIVE A series of novel Danshensu ester derivatives were rationally designed and synthesized by using the natural plant extract sodium danshensu as the starting material,and all the target compounds were evaluated for protective effects against the myocardial ischemia. METHODS Danshensu underwent reaction with different alcohols to get ester derivatives through ester bonds. These derivatives were evaluated in H9 c2 cells against oxygen deprivation induced injury to illustrate the structure-activity relationships. RESULTS All the sixteen ester derivatives were confirmed by ^1H NMR combined with MS. The pharmacological results showed that under the experimental concentration,some compounds exhibited higher boiological effect than Danshensu. CONCLUSION Derivatives modified at the carboxylic acid groups could keep higher pharmacological vactivity than simultaneously modified the phenolic hydroxyl groups.
出处
《海峡药学》
2018年第2期13-18,共6页
Strait Pharmaceutical Journal
关键词
丹参素
酯类衍生物
合成
抗心肌缺血
Danshensu
Ester derivative
Synthesis
Anti-myocardial ischemia
