环维黄杨星D的前药改造及生物活性研究

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。

Prodrug structural modifications of cyclovirobuxine D and their biological activity

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, suc 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.