Inhibition of xanthine oxidase by copper-gallate coordination polymers and its mechanistic study

文献类型： 外文期刊

第一作者： Mo, Yejian

作者： Mo, Yejian;Ren, Jian;Sun, Shili;Shen, Xiaoyu;Mo, Yejian;Ren, Jian;Liu, Kexin;Deng, Chunlin;Shen, Xiaoyu;Mo, Yejian;Ren, Jian;Liu, Kexin;Deng, Chunlin

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关键词： Hyperuricemia; Metal-polyphenol coordination polymers; Xanthine oxidase inhibitors; Antioxidant properties

期刊名称：JOURNAL OF MOLECULAR STRUCTURE （ 影响因子：4.7； 五年影响因子：4.0 ）

ISSN： 0022-2860

年卷期： 2025 年 1346 卷

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收录情况： SCI

摘要： Hyperuricemia (HUA) is a metabolic disease caused by elevated uric acid levels, with xanthine oxidase (XOD) as the key enzyme in uric acid production. Current treatments primarily use XOD inhibitors (e.g., allopurinol and febuxostat), but their lack of antioxidant activity limits their ability to counteract oxidative stress in HUA. Gallic acid (GA), a polyphenol with antioxidant properties, weakly inhibits XOD but is insufficient alone. Transition metal ions like Cu2* are potent reversible XOD inhibitors, yet excessive concentrations cause toxicity. The coordination reaction effectively reduces metal ion toxicity while partially preserving the inherent antioxidant properties of polyphenols. Using gallic acid (GA) as a ligand with Cu2*, we synthesized Cu-GA complex, which forms a stable coordination polymer that minimally releases free Cu2* in water. Cu-GA demonstrated superior XOD inhibition compared to allopurinol (AP), GA, and Cu2* alone, functioning as a reversible inhibitor to reduce uric acid levels. Additionally, it maintained significant antioxidant activity while showing substantially lower cytotoxicity in LO2 and AML12 cells than free Cu2*. In conclusion, for Cu-GA, the coordination reaction retained the inhibitory effect of Cu2+ on XOD, while conferring some antioxidant effects, and also reduced the biotoxicity of Cu2+.

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