title: Two 6-(propan-2-yl)-4-methyl-morpholine-2,5-diones as new non-purine xanthine oxidase inhibitors and anti-inflammatory agents.
abstract: Two cyclodidepsipeptides, 3-(2-methylpropyl)-6-(propan-2-yl)-4-methyl-morpholine-2,5-dione (1) and 3,6-di(propan-2-yl)-4-methyl-morpholine-2,5-dione (2), were evaluated for inhibitory activity against commercial enzyme xanthine oxidase (XO) in vitro and XO in rat liver homogenate as well as for anti-inflammatory response on human peripheral blood mononuclear cells (PBMCs). Both of cyclodidepsipeptides were excellent inhibitors of XO and significantly suppressed the nuclear factor of κB (NF-κB) activation. Allopurinol, a widely used XO inhibitor and drug to treat gout, relevated stronger inhibitory effect on rat liver XO activity than those of compounds 1 and 2. Molecular docking studies were performed to gain an insight into their binding modes with XO. The studied morpholine-diones derivatives exerting XO inhibition and anti-inflammatory effect may give a promise to be used in the treatment of gout and other excessive uric acid production or inflammatory conditions.
authors: Department of Pharmacy, Faculty of Medicine, University of Nis, Bulevar Dr. Zorana Djindjica 81, 18000 Nis, Serbia. a.smelcerovic@yahoo.com
authors: Andrija
authors: A
authors: Smelcerovic
authors: Miroslav
authors: M
authors: Rangelov
authors: Zaklina
authors: Z
authors: Smelcerovic
authors: Andrej
authors: A
authors: Veljkovic
authors: Emiliya
authors: E
authors: Cherneva
authors: Denitsa
authors: D
authors: Yancheva
authors: Goran M
authors: GM
authors: Nikolic
authors: Zivomir
authors: Z
authors: Petronijevic
authors: Gordana
authors: G
authors: Kocic
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D062105:Molecular Docking Simulation; D009000:Monocytes / Q000187:drug effects; D009025:Morpholines / Q000494:pharmacology*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
chemical_list: D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D009025:Morpholines; D014969:Xanthine Oxidase