title: Discovery and biological evaluation of some (1H-1,2,3-triazol-4-yl)methoxybenzaldehyde derivatives containing an anthraquinone moiety as potent xanthine oxidase inhibitors.
abstract: A series of (1H-1,2,3-triazol-4-yl)methoxybenzaldehyde derivatives containing an anthraquinone moiety were synthesized and identified as novel xanthine oxidase inhibitors. Among them, the most promising compounds 1h and 1k were obtained with IC50values of 0.6μM and 0.8μM, respectively, which were more than 10-fold potent compared with allopurinol. The Lineweaver-Burk plot revealed that compound 1h acted as a mixed-type xanthine oxidase inhibitor. SAR analysis showed that the benzaldehyde moiety played a more important role than the anthraquinone moiety for inhibition potency. The basis of significant inhibition of xanthine oxidase by 1h was rationalized by molecular modeling studies.
authors.affiliation: School of Pharmacy, China Medical University, 77 Puhe Road, North New Area, Shenyang 110122, China.
authors.forename: Ting-Jian
authors.initials: TJ
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, China Medical University, 77 Puhe Road, North New Area, Shenyang 110122, China.
authors.forename: Song-Ye
authors.initials: SY
authors.lastname: Li
authors.affiliation: School of Pharmacy, China Medical University, 77 Puhe Road, North New Area, Shenyang 110122, China.
authors.forename: Wei-Yan
authors.initials: WY
authors.lastname: Yuan
authors.affiliation: School of Pharmacy, China Medical University, 77 Puhe Road, North New Area, Shenyang 110122, China.
authors.forename: Qing-Xia
authors.initials: QX
authors.lastname: Wu
authors.affiliation: School of Pharmacy, China Medical University, 77 Puhe Road, North New Area, Shenyang 110122, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: School of Pharmacy, China Medical University, 77 Puhe Road, North New Area, Shenyang 110122, China.
authors.forename: Su
authors.initials: S
authors.lastname: Yang
authors.affiliation: School of Pharmacy, China Medical University, 77 Puhe Road, North New Area, Shenyang 110122, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Sun
authors.affiliation: School of Pharmacy, China Medical University, 77 Puhe Road, North New Area, Shenyang 110122, China. Electronic address: fhmeng@cmu.edu.cn.
authors.forename: Fan-Hao
authors.initials: FH
authors.lastname: Meng
mesh_terms: D000880:Anthraquinones / Q000737:chemistry*; D001547:Benzaldehydes / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D020128:Inhibitory Concentration 50; D007700:Kinetics; D062105:Molecular Docking Simulation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000880:Anthraquinones; D001547:Benzaldehydes; D004791:Enzyme Inhibitors; D014230:Triazoles; D014969:Xanthine Oxidase; C032175:benzaldehyde
keywords: Anthraquinone; Hyperuricemia; Xanthine oxidase