title: Two new isoxazolines from the husks of Xanthoceras sorbifolia Bunge.
abstract: Two new isoxazoline compounds, 1-oxa-2-azaspiro[4.5]dec-2-ene-8β-ol (1) and 1-oxa-2-azaspiro[4.5]dec-2-ene-8α-ol (2), were isolated from the husks of fruits of Xanthoceras sorbifolia Bunge and their structures were determined by spectroscopic analyses, including X-ray crystallography, HRESI-MS, UV, IR, and 1D and 2D NMR (HSQC, HMBC, NOESY) methods. Neither compound showed significant inhibitory effects on butyrylcholinesterase (BuchE) and acetylcholinesterase (AChE), nor the selected tumor cells growth. Based on an online activity prediction program (PASS ONLINE), the structures with isoxazoline skeletons were found to show potential anti-asthmatic (AM) and anti-anaphylaxis (AP) activities; moreover, compounds 1 and 2 were predicted to possess high affinities for many enzymes involved in AM and AP according to the RCSB Protein Data Bank. High-affinity binding to phosphodiesterase IV (PDE-4), an important inflammatory modulator in asthma, was demonstrated experimentally, beside that, the predicted structures based on compounds 1 and 2 were analyzed for PDE-4 interactions using the molecular docking methodology of Discovery Studio 3.0 (DS 3.0). The predicted structure 2A-6 exhibited much higher affinity and stability of PDE-4 binding than the clinical PDE-4 inhibitor rolipram.
authors.affiliation: a School of Biopharmaceutical and Chemical Engineering , Liaoning Institute of Science and Technology , Benxi 117004 , China.
authors.forename: Hui-Qi
authors.initials: HQ
authors.lastname: Ge
authors.affiliation: b Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education , Shenyang Pharmaceutical University , Shenyang 110016 , China.
authors.forename: Guo-Sheng
authors.initials: GS
authors.lastname: Wan
authors.affiliation: b Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education , Shenyang Pharmaceutical University , Shenyang 110016 , China.
authors.forename: Da
authors.initials: D
authors.lastname: Wang
authors.affiliation: b Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education , Shenyang Pharmaceutical University , Shenyang 110016 , China.
authors.forename: Ji-Ming
authors.initials: JM
authors.lastname: Wu
authors.affiliation: b Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education , Shenyang Pharmaceutical University , Shenyang 110016 , China.
authors.forename: Bo-Hang
authors.initials: BH
authors.lastname: Sun
authors.affiliation: c Key Laboratory of Cardiovascular Medicine Research of Ministry of Education , Harbin Medicinal University , Harbin 150081 , China.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Wu
authors.affiliation: b Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education , Shenyang Pharmaceutical University , Shenyang 110016 , China.|c Key Laboratory of Cardiovascular Medicine Research of Ministry of Education , Harbin Medicinal University , Harbin 150081 , China.
authors.forename: Hui-Yuan
authors.initials: HY
authors.lastname: Gao
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006801:Humans; D007555:Isoxazoles / Q000737:chemistry / Q000302:isolation & purification*; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D009828:Oleanolic Acid / Q000737:chemistry; D029631:Sapindaceae / Q000737:chemistry; D012503:Saponins / Q000737:chemistry; D013237:Stereoisomerism; D014315:Triterpenes / Q000737:chemistry
chemical_list: C000613129:1-oxa-2-azaspiro(4.5)dec-2-ene-8alpha-ol; D002800:Cholinesterase Inhibitors; D004365:Drugs, Chinese Herbal; D007555:Isoxazoles; D012503:Saponins; D014315:Triterpenes; D009828:Oleanolic Acid
keywords: Xanthoceras sorbifolia; activity prediction; docking analysis; isoxazoline; phosphodiesterase IV