Xanthine oxidase (XO) has been primarily targeted for the development of anti-hyperuriciemic /anti-gout agents as it catalyzes the conversion of xanthine and hypoxanthine into uric acid. XO overexpression in various cancer is very well correlated due to reactive oxygen species (ROS) production and metabolic activation of carcinogenic substances during the catalysis. Herein, we report the design and synthesis of a series of 3,5-diaryl-4,5-dihydro-1H-pyrazole carbaldehyde derivatives (2a-2x) as xanthine oxidase inhibitors (XOIs). A docking model was developed for the prediction of XO inhibitory activity of our novel compounds. Furthermore, our compounds anticancer activity results in low XO expression and XO-harboring cancer cells both in 2D and 3D-culture models are presented and discussed. Among the array of synthesized compounds, 2b and 2m emerged as potent XO inhibitors having IC values of 9.32 ± 0.45 µM and 10.03 ± 0.43 µM, respectively. Both compounds induced apoptosis, halted the cell cycle progression at the G1 phase, elevated ROS levels, altered mitochondrial membrane potential, and inhibited antioxidant enzymes. The levels of miRNA and expression of redox sensors in cells were also altered due to increase oxidative stress induced by our compounds. Compounds 2b and 2m hold a great promise for further development of XOIs for the treatment of XO-harboring tumors.
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http://dx.doi.org/10.1016/j.bioorg.2020.104620 | DOI Listing |
J Food Sci Technol
February 2025
Program of Medical Technology, Faculty of Allied Health Sciences, Chonburi, 20130 Thailand.
Unlabelled: The aim of this study was to utilize four rice pasta by-products (RPB), including white rice pasta, black jasmine rice pasta, red jasmine rice pasta and brown rice pasta, to ferment into four vinegars. The dynamic variations during fermentation and their quality were evaluated. During alcoholic fermentation, the saccharified substrates were fermented with for 12 days, resulting in an alcohol yield of approximately 10% (v/v) after 4 days of fermentation.
View Article and Find Full Text PDFCureus
December 2024
Diabetes and Endocrinology, Prabhath Diabetes Care Centre, Udupi, IND.
This meta-analysis investigates the potential of allopurinol to prevent contrast-induced nephropathy (CIN), a common and serious complication of percutaneous coronary intervention (PCI). CIN is particularly prevalent among high-risk populations, including patients with chronic kidney disease (CKD) or acute coronary syndrome (ACS), where the administration of contrast agents can exacerbate renal injury. Allopurinol, a xanthine oxidase inhibitor, is known for its dual action in reducing oxidative stress and uric acid production, positioning it as a promising therapeutic candidate to mitigate CIN.
View Article and Find Full Text PDFJ Nephrol
January 2025
School of Pharmacy and Institute of New Drug Development, Jeonbuk National University, Jeonju, 54907, Republic of Korea.
Background: The effect of lowering uric acid levels on renal function in patients with diabetic kidney disease remains unclear. Previous randomized controlled trials (RCTs) have reported conflicting results regarding the effects of xanthine oxidase inhibitors on renal function. This study aimed to examine the renoprotective effects of xanthine oxidase inhibitors (febuxostat and topiroxostat) in patients with diabetic kidney disease.
View Article and Find Full Text PDFAntioxidants (Basel)
January 2025
Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China.
Acute pancreatitis (AP) is a potentially fatal acute digestive disease that is widespread globally. Although significant progress has been made in the previous decade, the study of mechanisms and therapeutic strategies is still far from being completed. Xanthine oxidase (XO) is an enzyme that catalyzes hypoxanthine and xanthine to produce urate and is accompanied by the generation of reactive oxygen species (ROS) in purine catabolism.
View Article and Find Full Text PDFAntioxidants (Basel)
December 2024
Department of Pharmacognosy, Faculty of Pharmacy, Yeditepe University, Kayisdagi Cad., Atasehir, 34755 Istanbul, Türkiye.
Qualitative and quantitative differences in the chemical composition between bee pollen originated from (Türkiye and Slovenia), spp. (Türkiye and Slovenia), and spp. (Türkiye) and androecia of , , and (apetalous trees) were evaluated for the first time by new high-performance thin-layer chromatography (HPTLC) and ultra-performance liquid chromatography (UPLC) methods using marker compounds.
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