title: Design, synthesis and molecular modeling of aloe-emodin derivatives as potent xanthine oxidase inhibitors.
abstract: A series of aloe-emodin derivatives were synthesized and evaluated as xanthine oxidase inhibitors. Among them, four aloe-emodin derivatives showed significant inhibitory activities against xanthine oxidase. The compound 4,5-dihydroxy-9,10-dioxo-9,10-dihydroanthracene-2-carbaldehyde (A1) possessed the best xanthine oxidase inhibitory activity with IC50 of 2.79 μM. Lineweaver-Burk plot analysis revealed that A1 acted as a mixed-type inhibitor for xanthine oxidase. The docking study revealed that the molecule A1 had strong interactions with the active site of xanthine oxidase and this result was in agreement with kinetic study. Consequently, compound A1 is a new-type candidate for further development for the treatment of gout.
authors.affiliation: School of Ocean, Hainan University, Haikou 570228, People's Republic of China; School of Chemical Engineering, Huaihai Institute of Technology, Lianyungang 222005, People's Republic of China.
authors.forename: Da-Hua
authors.initials: DH
authors.lastname: Shi
authors.affiliation: School of Ocean, Hainan University, Haikou 570228, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: School of Ocean, Hainan University, Haikou 570228, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.affiliation: Marine Economic Research Center of Jiangsu, Huaihai Institute of Technology, Lianyungang 222005, People's Republic of China.
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Liu
authors.affiliation: School of Ocean, Hainan University, Haikou 570228, People's Republic of China. Electronic address: wangsf777@163.com.
authors.forename: Shi-Fan
authors.initials: SF
authors.lastname: Wang
mesh_terms: D000504:Aloe / Q000737:chemistry*; D000818:Animals; D000880:Anthraquinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D020134:Catalytic Domain / Q000187:drug effects; D002417:Cattle; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D062105:Molecular Docking Simulation; D013329:Structure-Activity Relationship; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: D000880:Anthraquinones; D004791:Enzyme Inhibitors; C518327:aloe emodin; D014969:Xanthine Oxidase
keywords: Aloe-emodin; Gout; Inhibitor; Xanthine oxidase