title: Discovery of novel xanthone derivatives as xanthine oxidase inhibitors.
abstract: Xanthine oxidase is the key enzyme that catalyzes the oxidation of hypoxanthine to xanthine and then to uric acid. In this study, a series of xanthone derivatives were synthesized as effective and a new class of xanthine oxidase inhibitor. Compounds 8a, 8c, 8i, 8g and 8r showed good inhibition against xanthine oxidase. The presence of a cyano group at the para position of benzyl moiety turned out to be the preferred substitution pattern. Molecular modeling studies were performed to gain an insight into its binding mode with xanthine oxidase, and to provide the basis for further structure-guided design of new non-purine xanthine oxidase inhibitors associated with the xanthone framework.
authors.affiliation: Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Hu
authors.forename: Honggang
authors.initials: H
authors.lastname: Hu
authors.forename: Weifeng
authors.initials: W
authors.lastname: Wu
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Chai
authors.forename: Jianfei
authors.initials: J
authors.lastname: Luo
authors.forename: Qiuye
authors.initials: Q
authors.lastname: Wu
mesh_terms: D000493:Allopurinol / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020134:Catalytic Domain; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*; D044004:Xanthones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D008024:Ligands; D044004:Xanthones; D000493:Allopurinol; C009689:xanthone; D014969:Xanthine Oxidase