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Aim: To search for compounds through structural modification of cyclovirobuxine D, using 20 or 21-aminosteroids as lead compound for the treatment of cerebrovascular diseases with better lipid peroxidation inhibitory activity., Methods: According to rational drug design principle, a series of cyclovirobuxine D analogues were prepared, and their bioactivities were tested., Results: Four new compounds were obtained and confirmed by spectra., Conclusion: Lipid peroxidation inhibitory effects of cyclovirobuxine D analogues were tested by using TBA method. Some compounds showed better activity than that of cyclovirobuxine D.

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.

Aim: To determine the effects of cyclovirobuxine D (CD) on intracellular Ca2+ mobilization and L-type Ca2+ current (I(Ca-L)) in isolated rat cardiomyocytes., Methods: The effects of CD on the amplitude of I(Ca-L) and intracellular Ca2+ mobilization induced by KCl and caffeine were studied with the method of patch-clamp technique and laser scanning confocal microscopy in rat ventricular myocytes., Results: CD decreased the amplitude of I(Ca-L) in a concentration-dependent manner. At 10 mV, 1 and 10 micromol x L(-1) CD decreased I(Ca-L) density from (- 9.9 +/- 1.8) pA/pF to (-6.4 +/- 1.4) and (-4.2 +/- 0.6) pA/pF, respectively. Confocal experiments showed that intracellular fluorescent intensity (FI) value of [Ca2+] in control resting level was not changed by 1 and 10 micromol x L(-1) CD. [Ca2+] increase in response to KCl could not be reduced by CD. The rise of [Ca2+]i in response to caffeine was further enhanced by pretreatment with CD., Conclusion: CD decreased I(Ca,L) in a concentration-dependent manner and increased [Ca2+]i release induced by caffeine in rat ventricular cardiomyocytes.

Aim: To search for new compounds for the treatment of cardiovascular diseases by structural modification of cyclovirobuxine D., Methods: According to rational drug design principle, a series of cyclovirobuxine D analogues were prepared, and their bioactivities were tested., Results: Ten new compounds were syntheized and confirmed by spectra., Conclusion: Endurance lacking oxygen activity and antiarrhythmia effects of some analogues of cyclovirobuxine D were tested. Some compounds showed better activity than cyclovirobuxine D.

Aim: To establish a RP-HPLC method for determination of cyclovirobuxine D., Methods: Cyclovirobuxine D reacted with a derivative reagent 1-naphthyl isocyanate in chloroform to form fluorescence derivatives, stopped the reaction by adding the mobile phase and then directly injected the solution into the chromatograph to seperate it by RP-HPLC. The analysis was carried out on C18 column, the mobile phase is methanol-water (85:15), the excitation wavelength was set at 305 nm, emission at wavelength 385 nm, and the flow rate was 1 mL.min-1. The effect of several factors including the reaction medium, temperature, time and amount of 1-naphthyl isocyanate on the yield of the derivatization was also investigated systematically., Results: A simple and rapid RP-HPLC method for the simultaneous isolation and analysis of cyclovirobuxine D and its related substances was developed, and the absence of interference between the derivative peak responses of cyclovirobuxine D and its related substances were verified by UV diode array detecter and MS. The linearity was obtained from 0.75 microgram.mL-1 to 2.5 micrograms.mL-1 of cyclovirobuxine D derivatives with a correlation coefficient of 0.9991. The detection limit of cyclovirobuxine D derivative was 1 ng.mL-1, the repeatability of derivatization was good with relative standard derivation no more than 1.2% and derivative was stable within 48 h. The method described conforms to the validation of China Pharmacopiea compendial methods used for pharmaceutical products in general., Conclusion: The established method is proved to be reliable quantitative method for the quality control of cyclovirobuxine D.