title: Biotransformation of bufadienolides by cell suspension cultures of Saussurea involucrata.
abstract: The biotransformation of three bioactive bufadienolides, namely, bufotalin (1), telocinobufagin (2), and gamabufotalin (3) by cell suspension cultures of Saussurea involucrata yielded 11 products. Bufotalin yielded 3-epi-bufotalin (1a), 3-epi-desacetylbufotalin (1b), 3-epi-bufotalin 3-O-β-D-glucoside (1c), 1β-hydroxybufotalin (1d), and 5β-hydroxybufotalin (1e); telocinobufagin yielded 3-dehydroscillarenin (2a), 3-dehydrobufalin (2b), and 3-epi-telocinobufagin (2c); and gamabufotalin yielded 3-epi-gamabufotalin (3a), 3-dehydrogamabufotalin (3b), and 3-dehydro-Δ¹-gamabufotalin (3c), respectively. Among these 11 products, 1a, 1b, 1c, 1d, 3a and 3c are previously unreported. The structures of these metabolites were elucidated based on NMR spectroscopic analyses and mass spectrometry. Most metabolites showed significant cytotoxic activities against human hepatoma (HepG2) and breast cancer (MCF-7) cell lines. In addition, the time course for the biotransformation of 3 was investigated.
authors.affiliation: The State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Ye
authors.forename: Yin-hui
authors.initials: YH
authors.lastname: Dong
authors.forename: Hong-bo
authors.initials: HB
authors.lastname: Hu
authors.forename: Si-Jia
authors.initials: SJ
authors.lastname: Tao
authors.forename: Jun
authors.initials: J
authors.lastname: Yin
authors.forename: De-an
authors.initials: DA
authors.lastname: Guo
mesh_terms: D001711:Biotransformation; D002018:Bufanolides / Q000737:chemistry / Q000493:pharmacokinetics*; D002316:Cardiotonic Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D010946:Plants, Medicinal / Q000378:metabolism; D030441:Saussurea / Q000378:metabolism*; D013997:Time Factors
chemical_list: D002018:Bufanolides; D002316:Cardiotonic Agents