Kinetic study on the inhibition of xanthine oxidase by acylated derivatives of flavonoids synthesised enzymatically

Abstract

Studies have reported that flavonoids inhibit xanthine oxidase (XO) activity; however, poor solubility and stability in lipophilic media limit their bioavailability and applications. This study evaluated the kinetic parameters of XO inhibition and partition coefficients of flavonoid esters biosynthesised from hesperidin, naringin, and rutin via enzymatic acylation with hexanoic, octanoic, decanoic, lauric, and oleic acids catalysed by Candida antarctica lipase B (CALB). Quantitative determination by ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) showed higher conversion yields (%) for naringin and rutin esters using acyl donors with 8C and 10C. Rutin decanoate had higher partition coefficients (0.95), and naringin octanoate and naringin decanoate showed greater inhibitory effects on XO (IC 50 of 110.35 and 117.51 lM, respectively). Kinetic analysis showed significant differences (p < .05) between the flavonoids before and after acylation regarding K m values, whereas the values for V max were the same, implying the competitive nature of XO inhibition. ARTICLE HISTORY

Advances in structures required of polyphenols for xanthine oxidase inhibition

“…Generally, the polyphenols has been indicated to inhibit XO in a competitive manner through binding to the active site of the enzyme, of which the inhibiting activities are directly proportional to their concentrations (de Araújo et al, 2017;Ren et al, 2019). Besides, it has also been revealed that some polyphenols inhibit XO in a noncompetitive or mixed way, which means that the molecular interactions may occur both in the active site of XO and the region around the molybdopterin cofactor (Honda et al, 2017).…”

“…The mechanism study usually depends on the kinetic and thermodynamics of the inhibition process, characterization of the conformation change of XO, and molecular docking study for simulating the interaction between the enzyme and substrate (Xiao, Kai, Yamamoto, & Chen, 2013; Xiao, Ni, Kai, & Chen, 2013; Xiao, Ni, Kai, & Chen, 2015). Generally, the polyphenols has been indicated to inhibit XO in a competitive manner through binding to the active site of the enzyme, of which the inhibiting activities are directly proportional to their concentrations (de Araújo et al., 2017; Ren et al., 2019). Besides, it has also been revealed that some polyphenols inhibit XO in a noncompetitive or mixed way, which means that the molecular interactions may occur both in the active site of XO and the region around the molybdopterin cofactor (Honda et al., 2017).…”

Screening and Evaluation of Xanthine Oxidase Inhibitors from Gnetum parvifolium in China

“…It could be seen through the plots that the mode of XO inhibition by piceatannol is competitive type and the modes of XO inhibition by rhaponiticin, resveratrol, and isorhapontigenin are uncompetitive type. The competitive inhibition means the Michaelis-Menten constant ( K m ) was increasing and the maximum reaction velocity ( V max ) remained unchanged, which indicates the occupation by inhibitor prevents substrate from connecting to the active site of enzyme [18]. The uncompetitive inhibition means both K m and V max are decreased, which indicates the inhibitor caused the inhibition by forming enzyme-substrate complex reversibly with weak interactions at a site other than the active site [19].…”

Determination of Urinary Caffeine Metabolites as Biomarkers for Drug Metabolic Enzyme Activities

“…Xanthine oxidase plays a crucial role in many drug metabolic processes, such as thiopurine drugs, containing 6-mercaptopurine, allopurinol, and uric acid, etc. [26,27,28,29]. Xanthine oxidase is important in gout patients, because XO produces uric acid, which is a crucial factor in gout.…”