College of Chemistry and Chemical Engineering, and Key Laboratory of Hunan Forest Products and Chemical Industry Engineering, Jishou University, Jishou 416000, PR China.
Eur J Med Chem. 2013 May;63:685-95. doi: 10.1016/j.ejmech.2013.03.016. Epub 2013 Mar 16.
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.
在一项基于黄酮类化合物的脲酶抑制剂的持续研究中，合成了 19 种黄酮类化合物的还原衍生物，并对其进行了针对幽门螺杆菌脲酶的活性评估。构效关系分析表明，4-脱氧类似物比其他还原产物更有效。在这些化合物中，4',7,8-三羟基-2-异黄酮（13）被发现是最有效的，其 IC50 为 0.85 μM，比市售的脲酶抑制剂乙酰羟肟酸（AHA）强 20 多倍。动力学研究表明，13 是 H. pylori 脲酶的竞争性抑制剂，Ki 值为 0.641 μM，这与分子对接的结果非常吻合。13 的生物学评价和作用机制研究表明，它是一种发现新型胃炎和胃溃疡药物的良好候选物。
