Article ID | Journal | Published Year | Pages | File Type |
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1399218 | European Journal of Medicinal Chemistry | 2013 | 11 Pages |
In a continuing study for discovering urease inhibitors based on flavonoids, nineteen reductive derivatives of flavonoids were synthesized and evaluated against Helicobacter pylori urease. Analysis of structure–activity relationship disclosed that 4-deoxy analogues are more potent than other reductive products. Out of them, 4′,7,8-trihydroxyl-2-isoflavene (13) was found to be the most active with IC50 of 0.85 μM, being over 20-fold more potent than the commercial available urease inhibitor, acetohydroxamic acid (AHA). Kinetics study revealed that 13 is a competitive inhibitor of H. pylori urease with a Ki value of 0.641 μM, which is well matched with the results of molecular docking. Biological evaluation and mechanism study of 13 suggest that it is a good candidate for discovering novel anti-gastritis and anti-gastric ulcer agent.
Graphical abstract4′,7,8-Trihydroxyl-2-isoflavene (13), derived from 4′,7,8-trihydroxylisoflavone is a potent Helicobacter pylori urease inhibitor with IC50 of 0.85 μM, and it is a pure competitive inhibitor with a Ki value of 0.641 μM.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Efficient methods were developed to access to 3-flavene and 2-isoflavene. ► 4-Deoxyflavonoids were determined as H. pylori urease inhibitors. ► The most active inhibitor showed IC50 over 20-fold lower than that of acetohydroxamic acid. ► Docking model and kinetic studies revealed a competitive inhibition mechanism.