[Prodrug structural modifications of cyclovirobuxine D and their biological activity].
OBJECTIVE
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.


CONCLUSIONS
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.
Deng
Lan
L
West China School of Pharmacy, Sichuan University, Chengdi 610041, China. denglan234@sina.com
Huang
Heng
H
Xu
Ming-Xia
MX
Zhou
Shi-Qing
SQ
Ren
Fang
F
Wang
Xing-Wen
XW
Li
Dai-Qing
DQ
D000157:Aconitine; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology*; D031235:Buxus / Q000737:chemistry; D002725:Chloroform; D004365:Drugs, Chinese Herbal / Q000138:chemical synthesis* / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D051379:Mice; D010946:Plants, Medicinal / Q000737:chemistry; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D000889:Anti-Arrhythmia Agents; D004365:Drugs, Chinese Herbal; D011355:Prodrugs; C032939:cyclovirobuxine D; D002725:Chloroform; D000157:Aconitine