title: Xanthine oxidase inhibitors from Garcinia esculenta twigs.
abstract: The EtOAc-soluble portion of the 80 % (v/v) EtOH extract from the twigs of Garcinia esculenta exhibited strong xanthine oxidase inhibition in vitro. Bioassay-guided purification led to the isolation of 1,3,6,7-tetrahydroxyxanthone (3) and griffipavixanthone (8) as the main xanthine oxidase inhibitors, along with six additional compounds (1, 2, 4-7), including two new compounds (1 and 2). This enzyme inhibition was dose dependent with an IC50 value of approximately 1.2 µM for 3 and 6.3 µM for 8. The inhibitory activity of 3 was stronger than the control allopurinol (IC50 value: 5.3 µM). To our knowledge, compound 8 is the first bixanthone that demonstrated potent XO inhibitory activity in vitro. The structures of the new compounds were established by spectroscopic analysis, and the optical properties and absolute stereochemistry of racemic (±) esculentin A (2) were further determined by the calculation of the DP4 probability and analysis of its MTPA ester derivatives.
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
authors.forename: Lun-Lun
authors.initials: LL
authors.lastname: Zhu
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
authors.forename: Wen-Wei
authors.initials: WW
authors.lastname: Fu
authors.affiliation: Kampo Research Laboratories, Kracie Pharma Ltd., Takaoka, Japan.
authors.forename: Shimpei
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
authors.forename: Yi-Nuo
authors.initials: YN
authors.lastname: Shao
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
authors.forename: Hong-Sheng
authors.initials: HS
authors.lastname: Tan
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Drug Research, Institute of Materia Medica, Shanghai Institutes for Biological Sciences, CAS, Shanghai, People's Republic of China.
authors.forename: Chang-Heng
authors.initials: CH
authors.lastname: Tan
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
authors.forename: Yan-Feng
authors.initials: YF
authors.lastname: Xiu
authors.affiliation: Kampo Research Laboratories, Kracie Pharma Ltd., Takaoka, Japan.
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Norimoto
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
authors.forename: Hong-Xi
authors.initials: HX
authors.lastname: Xu
mesh_terms: D004353:Drug Evaluation, Preclinical / Q000379:methods; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D029760:Garcinia / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*; D044004:Xanthones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology
chemical_list: C575656:1,3,6,7-tetrahydroxyxanthone; D004791:Enzyme Inhibitors; D044004:Xanthones; C000600533:griffipavixanthone; D014969:Xanthine Oxidase