【摘要】 目的通过对植物活性单体———环维黄杨星D的前药改造,以寻求疗效更好、治疗安全范围更宽的心血管药物。方法根据前药设计原理,设计合成目标化合物,并研究其生物活性。结果获得7个环维黄杨星D新衍生物,并经光谱证明其结构。结论选取部分环维黄杨星D新衍生物进行抗心律失常药理实验,结果表明部分化合物药理效果优于环维黄杨星D。更多还原

【Abstract】 Aim To search for compounds for the treatment of cardiovascular diseases through prodrug structural modifications of cyclovirobuxine D, a single efficient composition distilled from Box plant in China, which was used to treat angina and myocardial infarction. Methods According to prodrug design principle, a series of cyclovirobuxine D analogues were prepared, such as succinate, phosphate and amino acid ester, and their biological activities were tested. Results Seven new compounds were obtained and confirmed with ~1H NMR, MS, and element analysis. Conclusion In pharmacology experiment, for treating arrhythmia induced by aconitine, succinate and amino acid ester of cyclovirobuxine D (I and VII) showed better activities than that of cyclovirobuxine D. The normal rhythm of the heart duration of I and VII were (11.53±7.62) min and (12.68±9.25) min, compared with 0.9% NaCl solution and cyclovirobuxine D, (2.36±1.68) min and (10.25±6.59) min (P<0.01), respectively. Another pharmacology experiment, for treating arrhythmia induced by chloroform, the negative ratio of I and VII were 80% and 82%, compared with 0.9% NaCl solution and cyclovirobuxine D, 43% and 52% (P<0.05), respectively. The difference between new compounds and cyclovirobuxine D was distinct.更多还原