title: Identification, characterization, kinetics, and molecular docking of flavonoid constituents from Archidendron clypearia (Jack.) Nielsen leaves and twigs.
abstract: In our search for natural soluble epoxide hydrolase (sEH) inhibitors from plants, we found that the methanolic extract of the leaves and twigs of Archidendron clypearia (Jack.) Nielsen (Fabaceae) significantly inhibits sEH in vitro. In a phytochemical investigation of the water layer of A. clypearia, we isolated two new chalcones, clypesides A-B (1-2), 13 flavonoid derivatives (3-15) and established their structures based on an extensive 1D and 2D NMR, CD data, and MS analysis. All of the flavonoid derivatives inhibited sEH enzymatic activity in a dose-dependent manner, with IC50 values ranging from 10.0±0.4 to 30.1±2.1μM. A kinetic analysis of compounds 4, 8-10, 12, 13, and 15 revealed that the compounds 8-10 were non-competitive, 4, 13, and 15 were mixed-type, and 12 was competitive inhibitors. Additionally, molecular docking increased our understanding of their receptor-ligand binding. These results demonstrated that flavonoid derivatives from A. clypearia are potential sEH inhibitors.
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea; Institute of Marine Biochemistry (IMBC), Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Caugiay, Hanoi, Viet Nam.
authors.forename: Nguyen Phuong
authors.initials: NP
authors.lastname: Thao
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Bui Thi Thuy
authors.initials: BT
authors.lastname: Luyen
authors.affiliation: Department of Horticultural Environment, National Institute of Horticultural and Herbal Science, RDA, Wanju-gun 440-310, Republic of Korea.
authors.forename: Jang Hoon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Ah Reum
authors.initials: AR
authors.lastname: Jo
authors.affiliation: Institute of Marine Biochemistry (IMBC), Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Caugiay, Hanoi, Viet Nam.
authors.forename: Nguyen Tien
authors.initials: NT
authors.lastname: Dat
authors.affiliation: Institute of Marine Biochemistry (IMBC), Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Caugiay, Hanoi, Viet Nam.
authors.forename: Phan Van
authors.initials: PV
authors.lastname: Kiem
authors.affiliation: Institute of Marine Biochemistry (IMBC), Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Caugiay, Hanoi, Viet Nam.
authors.forename: Chau Van
authors.initials: CV
authors.lastname: Minh
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea. Electronic address: yhk@cnu.ac.kr.
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Kim
mesh_terms: D002942:Circular Dichroism; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors; D007887:Fabaceae / Q000737:chemistry*; D005419:Flavonoids / Q000737:chemistry* / Q000494:pharmacology; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D062105:Molecular Docking Simulation; D018515:Plant Leaves / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D005419:Flavonoids; D004851:Epoxide Hydrolases
keywords: Archidendron clypearia; Clypesides A–B; Flavonoid; Molecular docking; Soluble epoxide hydrolase