期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 60, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2022.128582
关键词
Xanthine oxidase inhibitors; Structural optimization; Ligand efficiency metrics
资金
- National Natural Science Foundation of China [81803355]
- Young Talents Program of China Medical University
In this study, a series of new compounds were designed, synthesized, and evaluated for their inhibitory activities against xanthine oxidase. Compound 9m showed the most potent inhibition, with a low IC50 value and favorable drug-like properties.
A series of 4-(phenoxymethyl)-1H-1,2,3-triazole derivatives were designed, synthesized, and evaluated for their xanthine oxidase (XO) inhibitory activities. Among these compounds, 9m emerged as the most effective XO inhibitor with an IC50 value of 0.70 mu M, which was approximately 14-fold more potent than allopurinol. Additionally, compound 9m displayed favorable drug-like properties with ligand efficiency (LE) and lipophilic ligand efficiency (LLE) values of 0.33 and 3.41, respectively. We further explored the binding mode of 9m in complex with XO by molecular docking and molecular dynamics studies. In vivo hypouricemic studies also suggested that 9m could effectively lower the serum uric acid levels of rat. In summary, compound 9m could be a promising lead for further development of XO inhibitors.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据