Synthesis, biological evaluation, and molecular docking studies of 2,5-substituted-1,4-benzoquinone as novel urease inhibitors

• Published in: Bioorganic & medicinal chemistry 2012-08, Vol.20 (16), p.4889-4894
• Main Authors: You, Zhong-Lu, Xian, Dong-Mei, Zhang, Mei, Cheng, Xiao-Shan, Li, Xiao-Fang
• Format: Article
• Language: English
• Subjects: active sites; Benzoquinone; benzoquinones; Benzoquinones - chemistry; Benzoquinones - pharmacology; Biological and medical sciences; Crystal structure; Crystallography, X-Ray; Dose-Response Relationship, Drug; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Helicobacter pylori; Helicobacter pylori - enzymology; Inhibition; inhibitory concentration 50; Medical sciences; Models, Molecular; Molecular docking; Molecular Structure; nuclear magnetic resonance spectroscopy; Pharmacology. Drug treatments; Structure-Activity Relationship; Urease; Urease - antagonists & inhibitors; Urease - metabolism; urease inhibitors; X-radiation
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2012.07.002

A series of 2,5-substituted-1,4-benzoquinone were prepared. The urease inhibitory activities and the molecular docking studies of the compounds against Helicobacter pylori urease were carried out. Three compounds bearing effective activities. A series of 2,5-substituted-1,4-benzoquinone (1–6) were prepared and structurally characterized by elemental analysis, IR spectra, 1H and 13C NMR spectra, and single crystal X-ray determination. The urease inhibitory activities of the compounds against H. pylori urease were studied. Among the compounds, 2,5-bis(2-morpholin-4-ylethylamino)-[1,4]benzoquinone (2) shows the most effective activity with IC50 value of 27.30±2.17μM. Docking simulation was performed to insert compound 2 into the crystal structure of H. pylori urease at the active site to determine the probable binding mode. As a result, compound 2 may be used as a potential urease inhibitor.