title: Integration of Multiple Analytical and Computational Tools for the Discovery of High-Potency Enzyme Inhibitors from Herbal Medicines.
abstract: Herbal medicines (HMs) are an important source of drugs. In this study, an efficient strategy integrating ultrafiltration LC-MS, microplate bioassays, and molecular docking was proposed to screen high-potency enzyme inhibitors from HMs. Using this strategy, the structure-activity relationships (SARs) including binding-affinity-based SAR, enzymatic-activity-based SAR, and structural-complementarity-based SAR of compounds in an HM can be analyzed to provide abundant information for drug discovery. A prominent advantage of the approach is that it offers a multidimensional perspective to understand enzyme-ligand interactions, which could help to avoid false-positive screening results brought by a single method. By using xanthine oxidase (XOD) as an illustrative case, two types of potent XOD inhibitors, including flavones and coumarins, were successfully screened out from an HM of Ginkgo biloba. The study is expected to set a solid foundation for multidisciplinary cooperation in drug discovery.
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Hui-Peng
authors.initials: HP
authors.lastname: Song
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Jin-Xiu
authors.initials: JX
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Qian
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Si-Qi
authors.initials: SQ
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Xin-Guang
authors.initials: XG
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
mesh_terms: D001665:Binding Sites; D001688:Biological Products / Q000737:chemistry / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003374:Coumarins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D047309:Flavones / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D020441:Ginkgo biloba / Q000737:chemistry / Q000378:metabolism; D029001:Herbal Medicine; D062105:Molecular Docking Simulation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship; D014462:Ultrafiltration; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D001688:Biological Products; D003374:Coumarins; D004791:Enzyme Inhibitors; D047309:Flavones; D014969:Xanthine Oxidase
keywords: drug discovery; lead compounds; liquid chromatography; natural products; structure-activity relationships