title: Separation and peroxisome proliferator-activated receptor-γ agonist activity evaluation of synthetic racemic bavachinin enantiomers.
abstract: Bavachinin, isolated from Psoralea corylifolia seeds, has been reported to demonstrate peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist activity. However, isolated bavachinin is actually a mixture of S and R configurations, with an enantiomeric excess value of approximately 24.3%. For further study on the structure-activity relationships of bavachinin, investigating the PPAR-γ agonist activity of the two enantiomers is crucial. Considering the limited availability, racemic bavachinin was prepared in this study using chemical synthesis. The enantiomers of racemic bavachinin were then separated using supercritical fluid chromatography. This concise strategy yielded (S)- and (R)-bavachinin in optical purity as high as ⩾97.5%. The PPAR-γ agonist activity of the two enantiomers was evaluated using a time-resolved fluorescence resonance energy transfer-based competitive binding assay method; IC50 values of (S)- and (R)-bavachinin were 616.7 and 471.2 nM, respectively. The interaction between the compounds and PPAR-γ was further explored using a molecular docking method. This study suggests that (S)- and (R)-bavachinin demonstrate similar PPAR-γ agonist activities.
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
authors.forename: Guoxin
authors.initials: G
authors.lastname: Du
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
authors.forename: Li
authors.initials: L
authors.lastname: Feng
authors.affiliation: Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Informatics Department, UCB Pharma, 216 Bath Road, Slough SL1 4EN, United Kingdom.
authors.forename: Jiye
authors.initials: J
authors.lastname: Shi
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
authors.forename: Fujiang
authors.initials: F
authors.lastname: Guo
authors.affiliation: Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China. Electronic address: wlzhu@simm.ac.cn.
authors.forename: Weiliang
authors.initials: W
authors.lastname: Zhu
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China. Electronic address: ymlius@163.com.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Li
mesh_terms: D001665:Binding Sites; D025924:Chromatography, Supercritical Fluid; D005419:Flavonoids / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D062105:Molecular Docking Simulation; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D029907:Psoralea / Q000737:chemistry / Q000378:metabolism; D012639:Seeds / Q000737:chemistry / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D047309:Flavones
chemical_list: D005419:Flavonoids; D047495:PPAR gamma; C468752:bavachinin; D047309:Flavones
keywords: Bavachinin; Binding assay; Molecular docking; PPAR-γ; Supercritical fluid chromatography