Inhibition of Xanthine Oxidase by 4-nitrocinnamic Acid: In Vitro and In Vivo Investigations and Docking Simulations


Дәйексөз келтіру

Толық мәтін

Аннотация

Background:Cinnamic acid and its derivatives have gained significant attention in recent medicinal research due to their broad spectrum of pharmacological properties. However, the effects of these compounds on xanthine oxidase (XO) have not been systematically investigated, and the inhibitory mechanism remains unclear.

Objective:The objective of this study was to screen 18 compounds and identify the XO inhibitor with the strongest inhibitory effect. Furthermore, we aimed to study the inhibitory mechanism of the identified compound.

Methods:The effects of the inhibitors on XO were evaluated using kinetic analysis, docking simulations, and in vivo study. Among the compounds tested, 4-NA was discovered as the first XO inhibitor and exhibited the most potent inhibitory effects, with an IC50 value of 23.02 ± 0.12 µmol/L. The presence of the nitro group in 4-NA was found to be essential for enhancing XO inhibition. The kinetic study revealed that 4-NA inhibited XO in a reversible and noncompetitive manner. Moreover, fluorescence spectra analysis demonstrated that 4-NA could spontaneously form complexes with XO, referred to as 4-NA‒XO complexes, with the negative values of △H and △S.

Results:This suggests that hydrogen bonds and van der Waals forces play crucial roles in the binding process. Molecular docking studies further supported the kinetic analysis and provided insight into the optimal binding conformation, indicating that 4-NA is located at the bottom outside the catalytic center through the formation of three hydrogen bonds. Furthermore, animal studies confirmed that the inhibitory effects of 4-NA on XO resulted in a significant reduction of serum uric acid level in hyperuricemia mice.

Conclusion:This work elucidates the mechanism of 4-NA inhibiting XO, paving the way for the development of new XO inhibitors.

Авторлар туралы

Jianmin Chen

School of Pharmacy and Medical technology, Putian University

Хат алмасуға жауапты Автор.
Email: info@benthamscience.net

Sijin Yu

School of Pharmacy and Medical technology, Putian University

Email: info@benthamscience.net

Zemin He

School of Pharmacy and Medical technology, Putian University

Email: info@benthamscience.net

Danhong Zhu

School of Pharmacy and Medical technology, Putian University

Email: info@benthamscience.net

Xiaozhen Cai

School of Pharmacy and Medical technology, Putian University

Email: info@benthamscience.net

Zhipeng Ruan

School of Pharmacy and Medical technology, Putian University

Email: info@benthamscience.net

Nan Jin

School of Pharmacy and Medical technology, Putian University

Email: info@benthamscience.net

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