Identification of cinobufagin metabolites in the bile of rats

Abstract

1. Cinobufagin (1) is a major bufadienolide in ChanSu (a traditional Chinese medicine) with a wide range of pharmacological activities. In this paper, the in vivo metabolites of 1 in rats were studied.

2. Nine metabolites were isolated from the bile of rats, and their structures were identified as: desacetylcinobufagin (2), 3-ketodesacetylcinobufagin (3), 3-epi-desacetylcinobufagin (4); 5β-hydroxy-3-epi-desacetylcinobufagin (5), 1α-hydroxy-3-epi-desacetylcinobufagin (6), 12β-hydroxy-3-epi-desacetylcinobufagin (7), 1β-hydroxy-3-epi-desacetylcinobufagin (8), 1α,5α-dihydroxy-3-epi-desacetylcino-bufagin (9), and 2α, 5β-dihydroxy-3-epi-desacetylcinobufagin (10), respectively, on the basis of widely spectroscopic studies including two-dimensional-nuclear magnetic resonance (NMR). Among them, metabolites 6–10 are new compounds.

3. The results show that hydroxylation is the main reaction involved in metabolism of 1, and the preferred hydroxylation sites were C-1 and C-5.

Keywords::

• Cinobufagin
• metabolites
• bufadienolide
• hydroxylation
• isomerization

Acknowledgements

The authors thank the National Natural Science Foundation of China (Grant Number 30701088) and the Bureau of Science & Technology of Dalian City (Grant Number 2008J23JH042) for financial support.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.