title: Functionalized magnetic nanoparticles coupled with mass spectrometry for screening and identification of cyclooxygenase-1 inhibitors from natural products.
abstract: Development of simple and effective methods for high-throughput, high-fidelity screening and identification of cyclooxygenase-1 (COX-1) inhibitors from natural products are important for drug discovery to treat inflammation and carcinogenesis. Here, we developed a new screening assay based on cyclooxygenase-1 (COX-1) functionalized magnetic nanoparticles (i.e. Fe3O4@SiO2-COX-1) for solid phase ligand fishing, and then mass spectrometry (MS) was applied for structural identification. Incubation conditions were optimized. High specificity for isolating COX-1 inhibitors was achieved by testing positive control, indomethacin, with active and inactive COX-1. Moreover, high stability of immobilized COX-1 (remained 95.3% after ten consecutive cycles) allows the analysis reproducible. When applied to turmeric extract, four curcuminoids (i.e. curcumin, demethoxycurcumin, bisdemethoxycurcumin, and 1-(4-hydroxy-3,5-dimethoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)-(1E,6E)-1,6-heptadiene-3,5-dione), difficult to be distinguished from original MS spectrum of turmeric extract, were isolated as main COX-1 inhibitors. Their structures were characterized based on their accurate molecular weight and diagnostic fragment ions. The results indicated that the proposed method was a simple, robust and reproducible approach for the discovery of COX-1 inhibitors from complex matrixes.
authors.affiliation: College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, China; Key Laboratory of Resources Chemistry of Nonferrous Metals, Central South University, Changsha 410083, China. Electronic address: shuyshi@gmail.com.
authors.forename: Shuyun
authors.initials: S
authors.lastname: Shi
authors.affiliation: College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, China.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Key Laboratory of Hunan Forest Products and Chemical Industry Engineering, Jishou University, Zhangjiajie 427000, China.
authors.forename: Mijun
authors.initials: M
authors.lastname: Peng
mesh_terms: D001688:Biological Products / Q000032:analysis* / Q000737:chemistry; D030024:Curcuma / Q000737:chemistry; D051545:Cyclooxygenase 1 / Q000737:chemistry* / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D055808:Drug Discovery; D057075:Enzyme Assays; D004800:Enzymes, Immobilized / Q000737:chemistry* / Q000378:metabolism; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D001688:Biological Products; D016861:Cyclooxygenase Inhibitors; D004800:Enzymes, Immobilized; D058185:Magnetite Nanoparticles; D010936:Plant Extracts; C012596:turmeric extract; D051545:Cyclooxygenase 1
keywords: Curcuminoid; Cyclooxygenase-1; Ligand fishing; MS; Turmeric