Prodrug structural modifications of cyclovirobuxine D and their biological activity

AimTo 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. MethodsAccording 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. ResultsSeven new compounds were obtained and confirmed with 1H NMR, MS, and element analysis. ConclusionIn 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.