title: Identification of cinobufagin metabolites in the bile of rats.
abstract: 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. Nine metabolites were isolated from the bile of rats, and their structures were identified as: desacetylcinobufagin (2), 3-ketodesacetylcinobufagin (3), 3-epi-desacetylcinobufagin (4); 5beta-hydroxy-3-epi-desacetylcinobufagin (5), 1alpha-hydroxy-3-epi-desacetylcinobufagin (6), 12beta-hydroxy-3-epi-desacetylcinobufagin (7), 1beta-hydroxy-3-epi-desacetylcinobufagin (8), 1alpha,5alpha-dihydroxy-3-epi-desacetylcino-bufagin (9), and 2alpha, 5beta-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. 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.
authors.affiliation: School of Pharmacy, Dalian Medical University, Dalian, China.
authors.forename: J
authors.initials: J
authors.lastname: Ning
authors.forename: T-H
authors.initials: TH
authors.lastname: Wu
authors.forename: Y
authors.initials: Y
authors.lastname: Tian
authors.forename: C-Y
authors.initials: CY
authors.lastname: Wang
authors.forename: G
authors.initials: G
authors.lastname: Tian
authors.forename: B-J
authors.initials: BJ
authors.lastname: Zhang
authors.forename: K-X
authors.initials: KX
authors.lastname: Liu
authors.forename: X-C
authors.initials: XC
authors.lastname: Ma
mesh_terms: D000818:Animals; D001646:Bile / Q000737:chemistry / Q000378:metabolism*; D002018:Bufanolides / Q000737:chemistry / Q000493:pharmacokinetics*; D002470:Cell Survival; D006367:HeLa Cells; D006801:Humans; D006900:Hydroxylation; D008516:Medicine, Chinese Traditional; D053858:Metabolic Networks and Pathways; D051381:Rats
chemical_list: D002018:Bufanolides; C002471:cinobufagin