title: Identification of the hydroxylated derivatives of bufalin: phase I metabolites in rats.
abstract: Bufalin was a typical bioactive bufadienolide, existed in the traditional Chinese medicine Chan Su with the high content of 1-5%. The in vivo metabolites (1-5) of bufalin were prepared by various chromatographic techniques from the bile samples of SD rats, which were administrated with bufalin orally. Their structures were determined on the basis of the widely spectroscopic data, including HRESIMS, 1D-, and 2D NMR. And 1-3, 5 were new compounds. In the in vitro cytotoxicity assay, metabolites (1-5) showed weaker cytotoxic effects than bufalin against human cancer cell lines A549 and H1299, which indicated that the metabolism was a significant pathway for the detoxification of bufalin. Structures analyses indicated that metabolites 1-5 were hydroxylated derivatives of bufalin. This study suggested that Phase I metabolism catalyzed by CYP450 enzymes was one of the metabolic ways of bufalin, which may promote the excretion of bufalin.
authors.affiliation: a College of Bioengineering, Beijing Polytechnic , Beijing 100029 , China.
authors.forename: Xiu-Lan
authors.initials: XL
authors.lastname: Xin
authors.affiliation: b College of Pharmacy , Dalian Medical University , Dalian 116044 , China.
authors.forename: Pei-Pei
authors.initials: PP
authors.lastname: Dong
authors.affiliation: c Chinese People's Liberation Army 210 Hospital , Dalian 116000 , China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Sun
authors.affiliation: b College of Pharmacy , Dalian Medical University , Dalian 116044 , China.
authors.forename: Sa
authors.initials: S
authors.lastname: Deng
authors.affiliation: d The Second Affiliated Hospital of Dalian Medical University , Dalian , 116044 , China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: b College of Pharmacy , Dalian Medical University , Dalian 116044 , China.|e State Key Laboratory of Bioactive Substance and Function of Natural Medicines , Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , 100050 , China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: b College of Pharmacy , Dalian Medical University , Dalian 116044 , China.
authors.forename: Xiao-Kui
authors.initials: XK
authors.lastname: Huo
authors.affiliation: a College of Bioengineering, Beijing Polytechnic , Beijing 100029 , China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Li
authors.affiliation: a College of Bioengineering, Beijing Polytechnic , Beijing 100029 , China.
authors.forename: Rong
authors.initials: R
authors.lastname: Lan
authors.affiliation: a College of Bioengineering, Beijing Polytechnic , Beijing 100029 , China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: d The Second Affiliated Hospital of Dalian Medical University , Dalian , 116044 , China.
authors.forename: Guang-Jun
authors.initials: GJ
authors.lastname: Fan
mesh_terms: D000818:Animals; D002018:Bufanolides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006801:Humans; D006900:Hydroxylation; D008297:Male; D008516:Medicine, Chinese Traditional; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002018:Bufanolides; C095591:chan su; C087925:bufadienolide; D003577:Cytochrome P-450 Enzyme System; C022777:bufalin
keywords: bile; bufalin; hydroxylation; in vivo; metabolites