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Anthocyanins, typical polyphenol compounds in grape skin, have attracted increasing interest due to their health-promoting properties. In this body of work, five representative anthocyanins (Cy-3-O-glc, Dp-3-O-glc, Pn-3-O-glc, Mv-3-O-glc, and Pt-3-O-glc) were studied using the density functional theory (DFT) to elucidate structure–radical scavenging activity in the relationship and the reaction path underlying the radical-trapping process. Based on thermodynamic parameters involved in HAT, SET-PT, and SPLET mechanisms, along with the structural attributes, it was found that the C4′ hydroxyl group mainly contributes to the radical scavenging activities of the investigated compounds. Pt-3-O-glc exhibits a good antioxidant capacity among the five compounds. The preferred radical scavenging mechanisms vary in different phases. For the Pt-3-O-glc compound, the calculations indicate the thermodynamically favoured product is benzodioxole, rather than o-quinone, displaying considerably reduced energy in double HAT mechanisms. Additionally, the thermodynamic and kinetic calculations indicate that the reaction of •OH into the 4′-OH site of Pt-3-O-glc has a lower energy barrier (7.6 kcal/mol), a higher rate constant (5.72 × 109 M−1 s−1), and exhibits potent •OH radical scavenging properties. Molecular docking results have shown the strong affinity of the studied anthocyanins with the pro-oxidant enzyme xanthine oxidase, displaying their significant role in inhibiting ROS formation. [ABSTRACT FROM AUTHOR]

Corn silk is a waste product when harvesting corn, but it contains many bioactive compounds. This research characterized and assessed the antioxidant bioactivity of compounds isolated from corn silk. Two different biological fermentation processes were compared: Solid-state fermentation (SSF) and submerged fermentation (SmF). Fresh corn silk (Zea mays L.) from both sweet corn and feed corn were fermented separately with various microorganisms (Bacillus subtilis, Lactobacillus sp. and Saccharomyces cerevisiae). Biological compounds were identified using LC-MS/MS. The extract was then tested for total phenolic content (TPC) and total flavonoid content (TFC). Next, the extract was tested for xanthine oxidase inhibition and antioxidant inhibition using the ABTS method. Potential contamination with the heavy metals As, Pb, and Hg was checked. The results show that fermented corn silk extract contains numerous bioactive compounds and amino acids. Among the different extract process variations, the highest TPC and TFC were 6.1 ± 0.7 µg GAE/g dry wt. and 68.3 ± 1.1 µg QE/g dry wt., respectively, and the highest xanthine oxidase inhibition was 76.5 ± 6.4 %. The above highest results were obtained using SmF of sweet corn for 60 days. In contrast, the highest antioxidant activity of 66.9 % was found using SSF of sweet corn for 20 days. Neither sweet corn nor feed corn were found to contain heavy metal ions. In summary, fermented corn silk extract samples contain numerous bioactive compounds, including both flavonoid and phenolic compounds, and the extract demonstrates antioxidant activity. Corn silk extracts from fermentation thus have potential for utilization in health products. [ABSTRACT FROM AUTHOR]

ABSTRACT: Hyperuricemia (HUA) is a metabolic disorder caused by excessive production of uric acid (UA) or impaired uric acid metabolism. Smilax China L. has a wide range of pharmacological activities such as immunomodulatory, anti-inflammatory, and antioxidant. Its roots and rhizomes have been widely used for the treatment of HUA. However, its mechanisms for treating HUA and reducing renal impairment have not been fully elucidated. In the present study, we evaluated the effect of Smilax China L. extract (SC) on UA metabolism and further explored its mechanism of action by feeding a high-calcium and high-protein diet to chickens to induce a model of HUA in chickens. SC significantly reduced serum UA levels and improved renal function in hyperuricemic chickens. Meanwhile, SC was able to inhibit the activity of xanthine oxidase (XOD) in vivo and in vitro, reducing the production of uric acid. In addition, SC was able to increase the expression of Breast Cancer Resistance Protein (BCRP) in the kidney and ileum and increase uric acid excretion. Therefore, our results suggest that SC may be a candidate for anti-hyperuricemia.

Anthocyanins, typical polyphenol compounds in grape skin, have attracted increasing interest due to their health-promoting properties. In this body of work, five representative anthocyanins (Cy-3-O-glc, Dp-3-O-glc, Pn-3-O-glc, Mv-3-O-glc, and Pt-3-O-glc) were studied using the density functional theory (DFT) to elucidate structure–radical scavenging activity in the relationship and the reaction path underlying the radical-trapping process. Based on thermodynamic parameters involved in HAT, SET-PT, and SPLET mechanisms, along with the structural attributes, it was found that the C4′ hydroxyl group mainly contributes to the radical scavenging activities of the investigated compounds. Pt-3-O-glc exhibits a good antioxidant capacity among the five compounds. The preferred radical scavenging mechanisms vary in different phases. For the Pt-3-O-glc compound, the calculations indicate the thermodynamically favoured product is benzodioxole, rather than o-quinone, displaying considerably reduced energy in double HAT mechanisms. Additionally, the thermodynamic and kinetic calculations indicate that the reaction of •OH into the 4′-OH site of Pt-3-O-glc has a lower energy barrier (7.6 kcal/mol), a higher rate constant (5.72 × 109 M−1 s−1), and exhibits potent •OH radical scavenging properties. Molecular docking results have shown the strong affinity of the studied anthocyanins with the pro-oxidant enzyme xanthine oxidase, displaying their significant role in inhibiting ROS formation.

This research describes the synthesis by an environmentally-friendly method, microwave irradiation, development and analysis of three novel and one previously identified Schiff base derivative as a potential inhibitor of bovine xanthine oxidase (BXO), a key enzyme implicated in the progression of gout. Meticulous experimentation revealed that these compounds (10, 9, 4, and 7) have noteworthy inhibitory effects on BXO, with IC50 values ranging from 149.56 µM to 263.60 µM, indicating their good efficacy compared to that of the standard control. The validation of these results was further enhanced through comprehensive in silico studies, which revealed the pivotal interactions between the inhibitors and the catalytic sites of BXO, with a particular emphasis on the imine group (-C = N-) functionalities. Intriguingly, the compounds exhibiting the highest inhibition rates also showcase advantageous ADMET profiles, alongside encouraging initial assessments via PASS, hinting at their broad-spectrum potential. The implications of these findings are profound, suggesting that these Schiff base derivatives not only offer a new vantage point for the inhibition of BXO but also hold considerable promise as innovative therapeutic agents in the management and treatment of gout, marking a significant leap forward in the quest for more effective gout interventions.

In this work, a series of novel compounds Spartinin C1-C24 were screened, synthesised and evaluated for inhibiting xanthine oxidase thus lowering serum uric acid level. The backbones were derived from the components of coastal marine source Spartina alterniflora and marketed drugs. The top hits Spartinin C10 & C22 suggested high inhibition percentages (78.54 and 93.74) at 10 μM dosage, which were higher than the positive control Allopurinol. They were low cytotoxic onto human normal hepatocyte cells. Treatment with Spartinin C10 could lower the serum uric acid level to 440.0 μM in the hyperuricemic model mice (723.0 μM), comparable with Allopurinol (325.8 μM). Spartinin C10 was more appreciated than Allopurinol on other serum indexes. The preliminary pharmacokinetics evaluation indicated that the rapid absorption, metabolism and elimination of Spartinin C10 should be further improved. The discovery of pharmaceutical molecules from coastal marine source here might inspire the inter-disciplinary investigations on public health. [ABSTRACT FROM AUTHOR]

An increase in gout prevalence has drawn attention among society and this situation drives the exploration of more favourable treatment using traditional medicinal plants which are rich in phenolic and flavonoid to avoid the side effects of modern medication. However, there are only few studies regarding the optimization of phytochemicals and anti-gout properties of medicinal plants and their combinations. The objectives of this study were to determine the optimal formulation of Strobilanthes crispus, Orthosiphon stamineus Benth and Stevia rebaudiana with maximum total phenolic and flavonoid contents as well as minimum IC50 of in vitro xanthine oxidase inhibitory activity and to examine their correlations among the formulations. Plant extracts from hot water infusion were tested for the total phenolic content, total flavonoid content and enzyme inhibition through Folin-ciocalteu assay, aluminium chloride method and xanthine oxidase inhibition assay, respectively. Simplex-centroid mixture design was applied in this study and 13 polyherbal formulations were generated by Design Expert Software. Linear, special cubic and quadratic models were selected to describe the interaction effect between polyherbal formulations and their responses. Low IC50 value (13.90 μg/mL) of xanthine oxidase activity was found in the binary combination of O. stamineus and S. rebaudiana and this probably related to its high phenolic and flavonoid contents as xanthine oxidase inhibition and phytochemicals were correlated. The suggested optimal formulation was comprised of 44.26 % O. stamineus and 55.74 % S. rebaudiana and it could be developed as an alternative treatment for gout. [ABSTRACT FROM AUTHOR]

Prenylated flavanones are a family of compounds with an important biological potential. Previously, anti-tyrosinase activity, acetylcholinesterase inhibitory activity, and neuroprotective effects of several prenyl flavanones isolated from different American Dalea genus species were reported. The biological potency of these kinds of compounds, together with the particularity of their chemical structures, encouraged us to investigate them for in vitro and in silico anti-xanthine oxidase activity. So, five prenyl-flavanones obtained from different Dalea sp (Dalea elegans, Dalea boliviana, and Dalea pazensis) were studied and the relationships between the structure of these prenyl-flavanones and their inhibitory activity were evaluated. Molecular docking studies were performed in order to propose the binding mode of the most active natural compound. 2′,4′-dihydroxy-5′-(1‴,1‴-dimethylallyl)-8-prenylpinocembrin (1) was the most active in this series showing an IC50 of 0.26 ± 0.07 µM comparable with the reference inhibitor, allopurinol. The presence of 5,7,2′,4′-tetrahydroxy substitution, accompanied by a prenyl group at 8-position in the A-ring, and a 5′ (1‴,1‴-dimethylallyl) were important to present a xanthine oxidase inhibitory activity. This fact was confirmed with molecular docking studies showing relevant interactions of 1 with the residues of the catalytic site of xanthine oxidase, and a binding energy of −7.3297 kcal mol−1. These results contributed not only to understanding the binding mode but also to validating the in vitro results. The obtained findings lead us to propose these prenyl-flavanones as lead compounds for the design and development of novel xanthine oxidase inhibitors for the treatment of diseases in which this enzyme is involved.

Abstract Background Despite the ongoing safety-driven spate of flavonoid xanthine oxidase (XOD) inhibition investigations, there is a lack of flavonoid-based uricostatic antihyperuricemic agents in clinical medicine. The poor pharmacokinetic profiles of glycosides (the natural form of existence of most flavonoids) relative to their aglycones could be largely responsible for this paradox. This investigation was aimed at providing both functional and molecular bases for the possible discovery of XOD inhibitory (or uricostatic) anti-hyperuricemic flavonoid aglycones from the leaves of a flavonoid-rich medicinal plant, Tribulus terrestris. To this end, the flavonoid aglycone fraction of T. terrestris leaf extract (FATT) was evaluated in vivo for antihyperuricemic activity in ethanol-induced hyperuricemic mice, monitoring serum and liver uric acid levels. Molecular docking and molecular dynamics simulation studies were carried out on the three major flavonoid aglycones of T. terrestris (isorhamnetin, quercetin and kaempferol) against an inhibitor conformation XOD model. The three flavonoids were also subjected to in vitro XOD activity assay, comparing their IC50 to that of allopurinol, a standard uricostatic antihyperuricemic drug. Results FATT significantly lowered serum uric acid (p

• Bioassay-guided fractionation of liquorice extract for tracing xanthine oxidase inhibitors was applied in this study. • Application of three sequential orthogonal separation techniques; partition for liquid-liquid fractionation followed by adsorption for gravity column chromatography and finally HPTLC for the eluted subfractions led to efficient separation of such complex mixture. • An orthogonal projection to latent structures (OPLS) model was implemented to correlate in-vitro xanthine oxidase inhibitory activity of different liquorice subfractions to their chemical matrices. • By using this integrated approach, it was possible to discover potent xanthine oxidase inhibitors from complex matrix of liquorice extract. Glycyrrhiza glabra L. roots are rich source of phytoconstituents for treatment of diverse illness. In this study, bioassay-guided fractionation of liquorice extract for tracing xanthine oxidase inhibitors using sequential three orthogonal separation techniques; partition for liquid-liquid fractionation followed by adsorption for gravity column chromatography and finally HPTLC for the eluted subfractions led to enhanced resolution and efficient separation of such complex mixture. Multivariate analysis of the resulting HPTLC images plot profiles of 34 liquorice subfractions having different polarities was modelled for the first time. An orthogonal projection to latent structures (OPLS) model was implemented to correlate in-vitro xanthine oxidase inhibitory activity of different liquorice subfractions to their chemical matrices exemplified by their chromatographic fingerprints. By using this integrated approach, we were able to discover potent xanthine oxidase inhibitors namely 7,4′-dihydroxyflavone (IC 50 =32.86 μM) and 3,3′,4,4′-tetrahydroxy-2-methoxychalcone (IC 50 =28.29 μM) from complex liquorice matrix. [ABSTRACT FROM AUTHOR]

Bioactive peptides have received significant attention due to their natural origin, low toxicity, and targeting specificity in the past decade. This study identified highly active ACE/XO inhibitors using molecular simulation and online databases and validated their in vitro antioxidant activity and the mechanisms of molecular interactions. According to computer predictions, Asp-Gly-Gly (DGG) and Asp-Gly-Met (DGGM) were identified as potential hydrolysates of common gastrointestinal peptidases with well water-soluble, non-toxic, and non-allergenic. Fourier transform infrared spectroscopy showed that the two peptides altered the enzyme's secondary structure, decreasing α-helix content by about 13 %, along with increasing β-sheet, randam coli, and β-turns content. Molecular docking and molecular dynamics simulations showed that hydrogen bonding and electrostatic interactions caused DGG and DGGM to form stable and dense complexes with the two enzymes. This study provides a new way for economical and efficient screening of new ACE and XO inhibitory peptides from natural proteins. • New ACE and XO inhibitory peptides in milk were screened and identified. • DGG showed stronger inhibitory activity against ACE than captopril in vitro. • The inhibitory activity of DGGM against XO was stronger than allopurinol in vitro. • Hydrogen bonding and electrostatic interactions enable DGG and DGGM to form stable and dense complexes with the two enzymes. [ABSTRACT FROM AUTHOR]

The roasting reaction products of ferulic and sinapic acids were analyzed using high-performance liquid chromatography (HPLC) and their constituent compounds were isolated. Structural analysis revealed that the major compounds were oligomers of the corresponding 4-vinylphenols. The xanthine oxidase (XO) inhibitory activity of the isolated compounds was also measured. Moderate XO inhibitory activity of some oligomers afforded from ferulic acid was observed. [ABSTRACT FROM AUTHOR]

Lignosus rhinocerotis (tiger milk mushroom), a sclerotium-forming mushroom, has been shown to have various pharmacological properties. However, its chemical constituents were not much investigated. In addition, its enzymes' inhibitory potentials are not yet described. Hence, the study aimed to investigate the chemical compositions of its sclerotium and fruiting body. The UPLC-QTOF-MS/MS was used to analyze ethanol and water extracts of both sclerotium and fruiting bodies. The ethanol extracts of the sclerotium and fruiting body were investigated for their antioxidant (DPPH and phosphomolybdenum) and enzymes (a-glucosidase, xanthine oxidase, and trypsin) inhibitory activities. The UPLC-QTOF-MS/MS analyses showed the presence of adenosine, chelidimerine, and pingpeimine B in the water extracts of the sclerotium and the fruiting body. Whereas cytidine, feroxin A, hirsuteine, mangiferin, neomangiferin and sophoraisoflavone A were identified in ethanol extracts of the sclerotium and the fruiting body. The fruiting body showed higher phenolic content than the sclerotium. The fruiting body also exhibited relatively higher radical scavenging and reducing activities, as well as a-glucosidase inhibition activities, when compared with the sclerotium. However, both the sclerotium and the fruiting body showed slight xanthine oxidase (compared to allopurinol) and trypsin inhibition activities. Findings provide a basis for further exploration of phytotherapeutic applications of L. rhinocerotis. [ABSTRACT FROM AUTHOR]

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. The analysis included eight studies encompassing a total of 929 patients undergoing PCI, with a mean age of 63 years. These studies compared the effects of allopurinol with placebo across varying doses and contrast agent types. The results demonstrated a significant reduction in CIN incidence with allopurinol, yielding a pooled odds ratio (OR) of 0.26 [95% CI (0.12, 0.56), P = 0.0006]. Despite the encouraging findings, moderate heterogeneity was observed (I² = 59%), likely arising from variations in study design, patient demographics, and the types of contrast agents used. Sensitivity analysis focusing on studies employing the contrast agent Omnipaque provided further support for the efficacy of allopurinol, with pronounced benefits observed in patients with CKD or ACS. These findings underline the potential of allopurinol as a preventive measure against CIN, especially in high-risk populations. However, the identified heterogeneity and inherent limitations of the included studies highlight the critical need for larger, well-designed randomized controlled trials to confirm these results, establish optimal dosing protocols, and explore the broader applicability of allopurinol in clinical practice., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Badreldin et al.)

Herein, we report the synthesis of platinum(II) complex bearing 3′-aminothiocyclohexanespiro-5′-hydantoin as ligand. The complex was characterized by IR, NMR spectral analyses, elemental analyses and density functional theory (DFT) calculations. Cytotoxicity and inhibitory potential on xanthine oxidase (XO) were evaluated by performed docking calculations. The cytotoxic activities of the 3′-aminothiocyclohexanespiro-5′-hydantoin (1), its Pt(II) complex (2), thiocyclohexanespiro-5′-hydantoin (3), and its platinum complex (4) were assessed against HL-60 and MDA-MB-231 cells in comparison with the antiproliferative activity of cisplatin as a referent. The ligands (1 and 3) did not exhibit in vitro antitumor efficacy on either of the human tumor cell lines. Complex 2 showed higher antitumor activity (IC50 = 42.1 ± 2.8 μM on HL-60 and 97.8 ± 7.5 μM against MDA-MB-231 cells) than complex 4 (IC50 = 89.6 ± 2.8 μM on HL-60 and 112.5 ± 4.2 μM in MDA-MB-231 cells). IC50 values of cisplatin as referent were 8.7 ± 2.4 μM on HL-60 and 31.6 ± 5.4 μM on MDA-MB-231 cell lines. The inhibitory activity of ligands and complexes against XO, evaluated in vitro, were compared with allopurinol (IC50 = 1.70 ± 0.51 μM) as standard inhibitor. The platinum(II) complexes (2 and 4) inhibited the activity of XO, with IC50 values 110.33 ± 26.38 μM and 115.45 ± 42.43 μM, respectively, while the ligands 1 and 3 did not show higher degrees of inhibition at concentrations lower than 150 μM. The inhibitory potential against XO might be a possible precedent resulting in improved profile and anticancer properties. [ABSTRACT FROM AUTHOR]

A series of novel substituted 2-(4-bromophenyl)-4-phenylthiazole compounds 5a–h were synthesized by a simplified two-step process. First, the selective and effective α-bromination of substituted acetophenone moieties with N-bromo succinamide was done followed by treating of substituted 2-bromo-1-phenylethan-1-one with 4-bromobenzothiamide under microwave irradiation. The structures of the newly synthesized compounds were confirmed by IR, 1H NMR, 13C NMR, mass spectra and C, H, N analysis. Further, all the synthesized compounds 5a–h were evaluated for xanthine oxidase inhibition. Among all the tested compounds, 5f was found to be highly potent (IC50 = 0.100 ± 0.08 µM) followed by 5e (IC50 = 0.145 ± 1.42 µM), compared to the standard allopurinol (IC50 = 0.150 ± 0.07 µM), which is evident from in vitro and in silico analysis. [ABSTRACT FROM AUTHOR]

Vietnamese people use mugwort (Artemisia vulgaris L.) to treat arthritis and gout. Our previous research shows that mugwort contains flavonoids, and its extract possesses antibacterial and anti-inflammatory activities. However, no publications have been on the xanthine oxidase inhibitory activity of mugwort and acute anti-inflammatory activity in vivo. The study aimed to verify the antioxidant, xanthine oxidase inhibitory, and anti-inflammatory capabilities of mugwort extract in vitro and in vivo , isolate phyto-compounds from potential bioactive fractions, and then evaluate their potential in inhibiting xanthine oxidase. According to established methods, the extract and the active flavonoids were obtained using different chromatographic techniques. DPPH, ABTS, reducing power, and H 2 O 2 elimination were used to evaluate antioxidant activity. The model of LPS-induced RAW264.7 cells was used to measure the inhibition of NO production. The carrageenan-induced paw oedema model was used to assess acute inflammation in mice. In vitro, xanthine oxidase inhibition assay was applied to investigate the effects of extract/compounds on uric acid production. Chemical structures were identified by spectral analysis. The assessment of the acute inflammatory model in mice revealed that both the 96% ethanol and the 50% ethanol extracts significantly decreased oedema in the mice's feet following carrageenan-induced inflammation. 96% ethanol extract exhibited a better reduction in oedema at the low dose. The analysis revealed that the ethyl acetate fraction had the highest levels of total polyphenols and flavonoids. Additionally, this fraction demonstrated significant antioxidant activity in various assays, such as DPPH, ABTS, reducing power, and H 2 O 2 removal. Furthermore, it displayed the most potent inhibition of xanthine oxidase, an anti-inflammatory activity. Five phytochemicals were isolated and determined from the active fraction such as luteolin (1), rutin (2), apigenin (3), myricetin (4), and quercetin (5). Except for rutin, the other compounds demonstrated the ability to inhibit effective xanthine oxidase compared to standard (allopurinol). Moreover, quercetin (5) inhibited NO production (IC 50 21.87 μM). The results indicate that extracts from A. vulgaris effectively suppressed the activity of xanthine oxidase and exhibited antioxidant and anti-inflammatory properties, potentially leading to a reduction in the production of uric acid in the body and eliminating ROS. The study identified mugwort extract and bioactive compounds derived from Artemisia vulgaris , specifically luteolin, apigenin, and quercetin, as promising xanthine oxidase inhibitors. These findings suggest that further development of these compounds is warranted. At the same time, the above results also strengthen the use of mugwort to treat gout disease in Vietnam. [Display omitted] • Ethanol 96% and 50% of mugwort extract indicate antioxidant, anti inflammatory, xanthine oxidase inhibition activities. • Ethanol 96% extract demonstrated an enhanced anti-inflammatory effect at low doses compared to ethanol 50% extract in vivo. • Ethyl acetate fraction contain highest amount of total polyphenol and flavonoid content. • Ethyl acetat fraction inhibit of xanthine oxidase, antioxidant and suppress NO production. • Five flavonoids isolated from ethyl acetat fraction can inhibit xanthine oxidase. [ABSTRACT FROM AUTHOR]

Peptides with xanthine oxidase (XOD)-inhibitory activities are potential dietary interventions for the treatment of hyperuricemia and gout. In this study, Macadamia integrifolia antimicrobial protein 2 (MiAMP2) was chosen for in silico proteolysis with pepsin, trypsin and chymotrypsin through ExPASy PeptideCutter, and the obtained peptides were further screened by water solubility, ADMET prediction and molecular docking. Four novel peptides, namely RPLY, PGPR, HGGR and GPY, were supposed to be non-toxic and have XOD-inhibitory potential. Molecular docking analysis showed that these peptides were able to bind to the active sites (such as Leu873, Phe914 and Thr1010) of XOD through interactions mainly including conventional hydrogen bond, alkyl and pi-interaction. These peptides were further synthesized to verify their in vitro XOD-inhibitory activities, and the IC50 values of PGPR, GPY and HGGR were shown to be 24.84 ± 0.02, 30.44 ± 0.33 and 24.89 ± 0.19 mM, respectively. Kinetic experiments demonstrated that PGPR and HGGR are mixed-type inhibitors, and GPY is a competitive inhibitor toward XOD with the inhibitory constant (Ki) values ranging from 1.09 to 8.98. Our results suggested that MiAMP2 is an important source of bioactive peptides for the management of hyperuricemia. [ABSTRACT FROM AUTHOR]

Momordica charantia [MC] is consumed as a vegetable and traditional medicine due to the presence of various bioactive compounds including charantin and coumarin which have anti-diabetic and anti-gout effects respectively. In this study, we investigated the effect of MC fermentation on its bioactivities. Anaerobic fermentation of Lactobacillus plantarum using MC extract with 10% soymilk at 30 °C increased charantin content to 13.46 ppm. Furthermore, α-amylase inhibition activity was increased to 64.75% and DPPH free radical scavenging ability to 47.14%, a 13.02%, and 11.68% increase, respectively. MC broth fermentation by Gluconacetobacter increased xanthine oxidase inhibition (XOI) activity by 30.77% on the 18th day of fermentation. Co-culture of Gluconacetobacter and S. cerevisiae increased XOI activity by 34.28% on the 12th day of fermentation. When compared to pure cultures, the multi-strain fermentation involving Gluconacetobacter , S. cerevisiae and L. plantarum increased XOI activity by 44.72% on the 6th day of fermentation and reduced fermentation time by 12 days. The results show that L. plantarum has an additive effect on XOI activity, whereas, S. cerevisiae works indirectly by producing alcohol which serves as a nutrient for Gluconacetobacter. [Display omitted] • Bioactivities of Momordica charantia (MC) was improved by microbial fermentation. • L. plantarum , Gloconacteobacter and yeast synergistically enhanced xanthine oxidase inhibition. • Multi-strain culture shortened fermentation time to six days. • L. plantarum fermentation of 10% soymilk added MC broth increased α-amylase inhibition. [ABSTRACT FROM AUTHOR]

In miso, due to the substantial presence of genistein, flazin is often overlapped and masked by genistein in HPLC analysis. Flazin in the miso extracts could be resolved with genistein through medium-pressure liquid chromatography run under a nonacidified methanol-water system and subsequently fractionated by semipreparative HPLC and identified by NMR spectroscopic analysis. As referenced, flazin was detected in all 11 locally marketed miso products, with contents ranging from 3.5 to 124.8 μg/g. In lab-made miso fermented at 28 and 37 °C for 8 weeks, flazin formed faster at 37 °C than at 28 °C. Based on the time-dependent HPLC chromatographic changes of the miso extracts during fermentation, the presence of tryptophan-derived ß-carboline intermediates was deduced. Tryptophan was then supplemented for miso fermentation, and four peak substances were targeted for isolation by sophisticated approaches. Four ß-carbolines were purified and instrumentally identified, i.e., P1: 1-(1,3,4,5-tetrahydroxypentyl)-9 H - pyrido[3,4- b ]indole, P2 (diastereomer of P1): 1-(1*,3,4,5-tetrahydroxypentyl)- 9 H -pyrido[3,4- b ]indole, and Miso 101: 1-(1,3,4,5-tetrahydroxypentyl)-9 H - pyrido[3,4- b ]indole 3-carboxylic acid, and Miso 111 (diastereomer of Miso 101): 1-(1*,3,4,5-tetrahydroxypentyl)-9 H -pyrido[3,4- b ]indole 3-carboxylic acid. Each of the purified β-carbolines along with tryptophan and flazin exhibited varied ABTS ·+ scavenging and xanthine oxidase inhibitory activities.

Introduction: Hyperuricemia is the key risk factor for gout, in which the elevated uric acid is attributed to the oxidation of hypoxanthine and xanthine to uric acid by xanthine oxidase (XO). Adverse effects of the current treatments lead to an urgent need for safer and more effective alternative from natural resources. Objective: To compare the metabolite profile of Chrysanthemum morifolium flower fraction with that of its detannified fraction in relation to XO inhibitory activity using a rapid and effective metabolomics approach. Methods: Proton nuclear magnetic resonance (1H‐NMR)‐based metabolomics approach coupled with multivariate data analysis was utilised to characterise the XO inhibitors related to the antioxidant properties, total phenolic, and total flavonoid contents of the C. morifolium dried flowers. Results: The highest XO inhibitory activity, 1,1‐diphenyl‐2‐picryl hydrazyl (DPPH) radical scavenging activity, total phenolic and flavonoid content with strong positive correlation between them were observed in the ethyl acetate (EtOAc) fraction. Detannified EtOAc showed higher XO inhibitory activity than non‐detannified EtOAc fraction. A total of 17 metabolites were tentatively identified, of which three namely kaempferol, 4‐hydroxybenzoic acid and apigenin, could be suggested to be responsible for the strong XO inhibitory activity. Additive interaction between 4‐hydroxybenzoic acid and apigenin (or kaempferol) in XO inhibition was demonstrated in the interaction assay conducted. Conclusion: Chrysanthemum morifolium dried flower‐part could be further explored as a natural XO inhibitor for its anti‐hyperuricemic potential. Metabolomics approach served as an effective classification of plant metabolites responsible for XO inhibitory activity, and demonstrated that multiple active compounds can work additively in giving combined inhibitory effects. Proton nuclear magnetic resonance (1H‐NMR)‐based metabolomics approach coupled with multivariate data analysis was utilised to compare the metabolite profile of Chrysanthemum morifolium flower fraction with that of its detannified fraction in relation to xanthine oxidase (XO) inhibitory activity. Detannified ethyl acetate (EtOAc) fraction showed higher XO inhibitory activity than non‐detannified EtOAc fraction. Kaempferol, 4‐hydroxybenzoic acid and apigenin were suggested to be responsible for the XO inhibitory activity. Additive interaction between 4‐hydroxybenzoic acid and apigenin (or kaempferol) in XO inhibition was demonstrated. [ABSTRACT FROM AUTHOR]

• Benzofuran were isolated from chloroform soluble fraction of Viburnum grandiflorum • Benzofuran caused significant xanthine oxidase inhibition with IC 50 :49.52 µM. • Docking simulations revealed that benzofuran interact with key amino acid residues through hydrogen and hydrophobic interactions. The study aimed to validate the folkloric medicinal uses of Viburnum grandiflorum. The column chromatography led to the isolation of a compound from the chloroform soluble fraction of V. grandiflorum which was characterized as 2, 3-dihydro-2-(4ʹ-hydroxy, 3ʹ-methoxyphenyl)-3-hydroxymethyl-5-(2-formylvinyl) 7-hydroxybenzofuran (benzofuran) on the basis of various spectroscopic techniques. When benzofuran was studied for xanthine oxidase inhibition, it caused significant concentration dependent inhibition of the enzyme with IC 50 : 49.52 µM, however, it was found less potent than standard xanthine inhibitor allopurinol (IC 50 : 0.59 µM). Binding orientation and binding energy of benzofuran and allopurinol were predicted via docking studies. Docking simulations revealed that both studied molecules interact with key amino acid residues through hydrogen bond (Arg 880, Glu 1261, Thr1010 with Allopurinol & Thr 1010 with benzofuran) and hydrophobic interactions (Phe914, Phe1009 with Allopurinol & Phe 910, Phe 1009 with benzofuran). A fair correlation between the computed binding energy and experimental values was observed. Thus, it is concluded that the isolated compound, benzofuran had inhibition on xanthine oxidase, need further detail studies. [ABSTRACT FROM AUTHOR]

The present study was to evaluate the two aminomethyl derivatives of dehydrozingerone: 5-[(4-methylpiperazin-1-yl)methyl]dehydrozingerone and 5-(morpholin-4-ylmethyl)dehydrozingerone as lipoxygenase and xanthine oxidase inhibitors. Nordihydroguaiaretic acid, allopurinol and the parent compound dehydrozingerone were used as comparative compounds. Results indicated that 5-[(4-methylpiperazin-1-yl)methyl] dehydrozingerone and 5-(morpholin-4-ylmethyl) dehydrozingerone inhibited the lipoxygenase enzyme with half-maximal inhibitory concentration of 219.13 and 269.39 µM, respectively. Their activities were comparable to nordihydroguaiaretic acid with a half-maximal inhibitory concentration of 216.84 µM. The compounds were also found to inhibit the xanthine oxidase enzyme with half-maximal inhibitory concentration of 102.34 and 230.52 µM, respectively, but their activities were lower than allopurinol with half-maximal inhibitory concentration of 34.09 µM. Dehydrozingerone was found inactive both as a lipoxygenase inhibitor and xanthine oxidase inhibitor. Besides, in silico study was carried out to predict the binding interaction between the enzymes and the compounds compared to each of positive controls. In conclusion, 5-[(4-methylpiperazin-1-yl)methyl] dehydrozingerone has lipoxygenase inhibitory activity comparable to nordihydroguaiaretic acid, but they have lower xanthine oxidase inhibitory activity than allopurinol. [ABSTRACT FROM AUTHOR]

Water and ethyl acetate extracts of sixteen galactogogue Thai medicinal plants collected in Northeastern Thailand were evaluated for the antioxidant activity in terms of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging property and total phenolic content (TPC), xanthine oxidase inhibitory and antibacterial activities. Among the extracts, both of the water and ethyl acetate extracts from the stem bark of Caesalpinia sappan (CS) and Ochna integerrima (OI) exhibited potent DPPH radical scavenging capacity (IC50 9.47 ± 0.59 - 13.25 ± 0.52 µg/mL) as compared to ascorbic acid (IC50 5.39 ± 0.32 µg/mL) and high TPC (632.89 ± 10.18 - 985.34 ± 0.76 mg gallic acid equivalent (GAE)/g of extract). The strongest xanthine oxidase inhibitory property was detected in the ethyl acetate extract from the root of Clausena harmandiana (CH) followed by CS and OI extracts showing %inhibition of 99.22 ± 0.22, 78.00 ± 0.79 and 68.67 ± 1.14, respectively, at the tested concentration of 50 µg/mL and referenced to allopurinol. The water extracts of CS and OI also possessed good antibacterial activity against eight tested pathogenic bacteria especially Gram-positive, S. aureus (MSSA) DMST 2933, S. aureus (MRSA) DMST 20651 and Bacillus cereus ATCC 1 1 7 7 8, with the MIC and MBC values ranging from 0.39 - 1.56 mg/mL. The antibacterial property of OI extract and xanthine oxidase inhibitory activity of CH and OI extracts were first reported. [ABSTRACT FROM AUTHOR]

Xanthine oxidase (XO) is a versatile metalloflavoprotein enzyme that is best known for its rate-limiting role in the purine degradation pathway. Therapeutic inhibition of XO is based on its role in a variety of diseases that is attributed either to the hyperproduction of uric acid, or the hyperproduction of reactive oxygen species. Herein, we report the assessment of XO inhibitory properties of 24 1,2,3,4-tetrahydroisoquinoline derivatives, among which compound 16 exhibited IC50 value of 135.72 ± 2.71 μM. The interaction of compound 16 with XO enzyme was simulated using the Site Finder module, molecular docking and molecular dynamics. Molecular modeling suggests that interactions with Met 1038, Gln 1040, Thr 1077, Gln 1194 and Val 1259 are an important factor for inhibitor affinity toward the XO enzyme. Our proposed binding model might be beneficial for the discovery of new active 1,2,3,4-tetrahydroisoquinoline-based inhibitors of XO enzyme. [ABSTRACT FROM AUTHOR]

The modulation of xanthine oxidase (XO) activity is critical to the treatment of hyperuricemia and oxidative stress-related disease. Although the walnut protein hydrolysates had been reported to inhibit XO, their interaction mechanism remained unclear. Herein, the walnut protein-derived peptides were used to evaluate their in vitro XO-inhibitory activity and their inhibitory mechanism. The results suggested that Trp-containing walnut protein-derived peptides were able to effectively inhibit XO, moreover, the increased number of Trp would significantly enhance the XO-inhibitory activity of Trp-containing peptides. Similar to the allopurinol, Trp had active interaction with the critical residues Glu802, Leu873, Ser876, Arg880, Phe914, Phe1009, Thr1010, Val1011, Leu1014, Ala1078, Ala1079 and molybdopterin MOS3004 of XO, making Trp-containing peptide have high XOI activity. Simultaneously, the Trp-containing walnut protein-derived peptide also had been found to show great potential in antioxidant activity. Present work would introduce functional food-derived peptides for the improvement of hyperuricemia and oxidative stress-related disease.

[Display omitted] This research describes the synthesis by an environmentally-friendly method, microwave irradiation, development and analysis of three novel and one previously identified Schiff base derivative as a potential inhibitor of bovine xanthine oxidase (BXO), a key enzyme implicated in the progression of gout. Meticulous experimentation revealed that these compounds (10 , 9 , 4 , and 7) have noteworthy inhibitory effects on BXO, with IC50 values ranging from 149.56 µM to 263.60 µM, indicating their good efficacy compared to that of the standard control. The validation of these results was further enhanced through comprehensive in silico studies, which revealed the pivotal interactions between the inhibitors and the catalytic sites of BXO, with a particular emphasis on the imine group (-C = N-) functionalities. Intriguingly, the compounds exhibiting the highest inhibition rates also showcase advantageous ADMET profiles, alongside encouraging initial assessments via PASS, hinting at their broad-spectrum potential. The implications of these findings are profound, suggesting that these Schiff base derivatives not only offer a new vantage point for the inhibition of BXO but also hold considerable promise as innovative therapeutic agents in the management and treatment of gout, marking a significant leap forward in the quest for more effective gout interventions. [ABSTRACT FROM AUTHOR]

A series of 22 compounds of thiazole-5-carboxylic acid derivatives was rationally designed and synthesized. All the compounds were characterized by using 1H and 13C NMR and tested against xanthine oxidase enzyme by spectrophotometric assay. Majority of the compounds were found active against the enzyme amongst which GK-20 with an IC50 value of 0.45 µM was found to be most potent. Structure-activity relationship obtained from the biological results revealed that the di-substituted compounds as Ring B were more potent than that of mono-substituted derivatives. Para-substitution on Ring B is crucial for the xanthine oxidase inhibitory potential. Enzyme kinetic studies further revealed their mixed type inhibition behavior. Moreover, the binding pattern of the most potent compound GK-20 within the febuxostat binding site of the enzyme was further analyzed by using docking studies which revealed that it sufficiently block the catalytic active site, which prevents the substrate to bind. [ABSTRACT FROM AUTHOR]

Xanthine oxidase (XOD) inhibitory activities of five dietary flavonoids pinobanksin, galangin, pinocembrin, pinocembrin-7-O-β-d-glucopyranoside and glabranin were evaluated. Enzyme kinetic studies and molecular docking simulation were conducted to investigate the mechanisms underlying the inhibitory activities. The results showed that these flavonoids exhibited excellent inhibitory activities (which were ranked in the order of pinobanksin > galangin > pinocembrin > pinocembrin-7-O-β-d-glucopyranoside > glabranin). Competitive inhibition and a mixed-type of competitive–noncompetitive inhibition were observed. The mode of inhibition was dependent on the type and concentration of the substrate and inhibitor. Fluorescence quenching data suggested that these flavonoids could interact with XOD at more than one binding site. The docking simulation revealed that galangin and pinobanksin could enter into the active site of XOD and form hydrogen bonding with amino acid residues (such as Ser-876, Asn-768, Glu-1261 and Thr-1010) and sandwiching aromatic interactions (π–π interactions) around the active site of XOD.

Xanthine oxidase is a frontier enzyme to produce oxidants, which leads to inflammation in the blood. Prenylated isoflavones from Flemingia philippinensis were found to display potent inhibition against xanthine oxidase (XO). All isolates (1–9) inhibited XO enzyme with IC50 ranging 7.8~36.4 μM. The most active isoflavones (2–5, IC50 = 7.8~14.8 μM) have the structural feature of a catechol motif in B-ring. Inhibitory behaviors were disclosed as a mixed type I mode of inhibition with KI < KIS. Binding affinities to XO enzyme were evaluated. Fluorescence quenching effects agreed with inhibitory potencies (IC50s). The compounds (2–5) also showed potent anti-LDL oxidation effects in the thiobarbituric acid-reactive substances (TBARS) assay, the lag time of conjugated diene formation, relative electrophoretic mobility (REM), and fragmentation of apoB-100 on copper-mediated LDL oxidation. The compound 4 protected LDL oxidation with 0.7 μM in TBARS assay, which was 40-fold more active than genistein (IC50 = 30.4 μM).

The white beetroot cv. Śnieżna Kula is the first betanin-free beetroot registered in the European Union. The aim of this study was to compare the phenolic acids profile and antioxidant capacity of leaves of white (SK) and red (CC) beetroots and red (LC) and white (BL) Swiss chard growing in Poland. LC leaves were the richest source of total phenolics (16.55 mg GAE/g FW) and phenolic acids (1.81 mg/g FW), while the highest content of flavonoids was determined in CC leaves (1.6 mg QE/g FW). The highest antiradical activity was observed for LC, whereas CC extract exhibited the highest chelating power. BL and CC leaf extracts demonstrated high LOX inhibitory potential (EC50 = 53.23 and 56.97 mg FW/mL, respectively). An uncompetitive type of LOX inhibition was obtained for all extracts. SK extracts demonstrated the highest XO inhibitory activity (EC50 = 81.04 mg FW/mL). A noncompetitive type of XO inhibition was obtained in both extracts from red leaves (CC and LC), whereas an uncompetitive mode of inhibition was observed in the case of white leaf (SK and LC) extracts. Thus, it can be assumed that the presence of betanin influences the XO inhibition mechanism.

Gout is a type of arthritis that causes painful inflammation in one or more joints. In gout, elevation of uric acid in the blood triggers the formation of crystals, causing joint pain. Malaysia is a mega-biodiversity country that is rich in medicinal plants species. Therefore, its flora might offer promising therapies for gout. This article aims to systematically review the anti-gout potential of Malaysian medicinal plants. Articles on gout published from 2000 to 2017 were identified using PubMed, Scopus, ScienceDirect, and Google Scholar with the following keyword search terms: “gout,” “medicinal plants,” “Malaysia,” “epidemiology,” “in vitro,” and “in vivo.” In this study, 85 plants were identified as possessing anti-gout activity. These plants had higher percentages of xanthine oxidase inhibitory activity (>85%); specifically, the Momordica charantia, Chrysanthemum indicum, Cinnamomum cassia, Kaempferia galanga, Artemisia vulgaris, and Morinda elliptica had the highest values, due to their diverse natural bioactive compounds, which include flavonoids, phenolics, tannin, coumarins, luteolin, and apigenin. This review summarizes the anti-gout potential of Malaysian medicinal plants but the mechanisms, active compounds, pharmacokinetics, bioavailability, and safety of the plants still remain to be elucidated.

Graphical abstract Highlights • Trp-containing walnut peptides inhibited xanthine oxidase. • Peptide enhanced xanthine oxidase inhibition with increasing number of Trp residues. • Molecular docking of XO with 20 amino acids, 400 dipeptides and 8000 tripeptides. • Trp-containing peptides had high antioxidant activity. Abstract The modulation of xanthine oxidase (XO) activity is critical to the treatment of hyperuricemia and oxidative stress-related disease. Although the walnut protein hydrolysates had been reported to inhibit XO, their interaction mechanism remained unclear. Herein, the walnut protein-derived peptides were used to evaluate their in vitro XO-inhibitory activity and their inhibitory mechanism. The results suggested that Trp-containing walnut protein-derived peptides were able to effectively inhibit XO, moreover, the increased number of Trp would significantly enhance the XO-inhibitory activity of Trp-containing peptides. Similar to the allopurinol, Trp had active interaction with the critical residues Glu802, Leu873, Ser876, Arg880, Phe914, Phe1009, Thr1010, Val1011, Leu1014, Ala1078, Ala1079 and molybdopterin MOS3004 of XO, making Trp-containing peptide have high XOI activity. Simultaneously, the Trp-containing walnut protein-derived peptide also had been found to show great potential in antioxidant activity. Present work would introduce functional food-derived peptides for the improvement of hyperuricemia and oxidative stress-related disease. [ABSTRACT FROM AUTHOR]

Highlights • Tuna protein hydrolysate (TPH) obtained by Alcalase was anti-hyperuricemic in rats. • Ethanol-soluble fraction (ESF) of TPH had peptides <1000 Da (13 di-/tri-peptides). • Xanthine oxidase (XO) inhibition: ESF > TPH > ethanol-insoluble fraction. • Phenylalanine (Phe)-di/tri-peptides are XO inhibitors (Phe-histidine is strongest). • 2 H-bonds and 1 π-π stacking with Phe-914 in XO affect XO-peptide inhibitor binding. Abstract This study follows recent attempts to discover natural xanthine oxidase (XO) inhibitors from foods, focusing herein on under-researched fish proteins. The anti-hyperuricemic function of tuna flesh hydrolysate (TPH) produced using Alcalase 2.4L was confirmed in potassium oxonate-induced hyperuricemic rats. TPH was separated using 80 wt% aqueous ethanol. The ethanol-soluble fraction (ESF) abundant in small peptides (<1000 Da) afforded the highest XO inhibition. Separation of ESF by Sephadex G-15 and UPLC/MS/MS revealed 13 di-/tri-peptides (12 are newly identified XO inhibitors). Their XO inhibitory activities were assessed using corresponding synthetic peptides via an improved HPLC method. Results indicate that Phe-containing peptides were more potent XO inhibitors than Trp-containing peptides, with Phe-His having the highest XO inhibitory activity (IC 50 = 25.7 mM). Molecular docking studies revealed the importance of two hydrogen bonds and one π-π stacking interaction with Phe-914 in XO for XO-peptide inhibitor binding. Phe-containing di-/tri-peptides could be potent XO inhibitors against hyperuricemia. [ABSTRACT FROM AUTHOR]

The stability of 20 different types of polyphenols that are constituents of edible plants was evaluated under different pH conditions (in buffer solutions at pH 6.8, 7.4, and 8.3). Carnosol was the most unstable, followed by myricetin, quercetin, carnosic acid, nordihydroguaiaretic acid, baicalein, gallic acid, and hydroxytyrosol. They were more unstable at a higher pH, which may be attributed to their enhanced redox properties in alkaline solutions, determined by their antioxidant and prooxidant activity. The xanthine oxidase (XO) inhibitory activity of the reaction products under alkaline conditions was evaluated. XO activity was significantly inhibited by the product produced from gallic acid in pH 7.4 solution. The structural analysis of this reaction product revealed that a gallic acid dimer, purpurogallin-8-carboxylic acid, was formed and played a role in the resulting XO inhibitory activity. [ABSTRACT FROM AUTHOR]

Abstract Xanthine oxidase (XO) is an interesting target for the synergic treatment of several diseases. Coumarin scaffold plays an important role in the design of efficient and potent inhibitors. In the current work, twenty 3-arylcoumarins and eight 3-heteroarylcoumarins were evaluated for their ability to inhibit XO. Among all the candidates, 5,7-dihydroxy-3-(3′-hydroxyphenyl)coumarin (compound 20) proved to be the best inhibitor with an IC 50 of 2.13 μM, being 7-fold better than the reference compound, allopurinol (IC 50 = 14.75 μM). To deeply understand the potential of this compound, the inhibition mode was also evaluated. Compound 20 showed an uncompetitive profile of inhibition. Molecular docking studies were carried out to analyze the interaction of compound 20 with the studied enzyme. The binding mode involving residues different from the catalytic site of the binding pocket, is compatible to the observed uncompetitive inhibition. Compound 20 was not cytotoxic at its IC 50 value, as demonstrated by the viability of 99.1% in 3 T3 cells. Furthermore, pharmacokinetics and physicochemical properties were also calculated, which corroborated with the potential of the studied compounds as promising XO inhibitors. [ABSTRACT FROM AUTHOR]

Abstract The inhibitory activity of xanthine oxidase (XO) is a combination of uric acid formation inhibition and superoxide anion (O 2 −) generation suppression. The inhibition of uric acid formation by XO is useful for the screening of natural compounds that prevent gout, while the suppression of O 2 − generation is useful for treating oxidative stress. Many edible plants contain abundant phenolic compounds and alk(en)yl phenols, and some of these compounds display XO inhibitory activity. This review focuses on XO inhibitory activity since this activity is used to characterize natural products. Recently, it was demonstrated that the inhibitory activity could be characterized using assays for XO inhibition, the suppression of O 2 − generation, DPPH radical scavenging and O 2 − radical scavenging. The inhibitory activity was divided three reaction types. The first is XO inhibition, the second O 2 − generation suppression by modification of enzyme molecules and the third two forms of O 2 - scavenging. It was demonstrated that these three activities are related to both the hydroxy group arrangement in the phenol portion and the alk(en)yl chains. This characterization is useful for pursuing XO inhibitors and antioxidants in natural compounds. Graphical abstract Inhibitory effect on xanthine oxidase by alk(en)yl phenols and related compounds was characterized. [A]: Uric acid formation inhibition, [B]: the enzyme molecule modification, [C]: O 2 − scavenging. Image Highlights • XO inhibitory activity was characterized using phenolic compounds. • The O 2 − suppression was affected by XO inhibition, reduction of the enzyme and O 2 − scavenging activity. • Reduction of the enzyme induced the suppression of O 2 − generation. • O 2 − Scavenging activity was divided into two types of activities. [ABSTRACT FROM AUTHOR]

The products from the thermal reaction of chlorogenic and caffeic acids, which is a model process of roasting coffee beans, exhibited xanthine oxidase (XO) inhibitory activity. From caffeic acid, six inhibitory phenylindanes were identified, and a new phenylindane displayed the highest inhibitory activity among them. The activity of these phenylindanes may contribute to XO inhibition-related functions of roasted coffee beverages. [ABSTRACT FROM AUTHOR]

5-Aryl-1 H -tetrazoles ( 1 – 24 ) were synthesized and screened for their xanthine oxidase (XO) inhibitory activity using allopurinol as standard inhibitor (IC 50  = 2.0 ± 0.01 µM). Six compounds 3 , 4 , 5 , 9 , 21 , and 24 exhibited significant to weak activities with IC 50 values in the range of 7.4–174.2 µM. Active compounds were further subjected to kinetic and molecular docking studies to deduce their modes of inhibition, and to study their interactions with the protein (XO) at atomic level, respectively. Interestingly, all these compounds showed a competitive mode of inhibition. Docking studies identified several important interactions between the ligand and the receptor protein (XO). Some of these interactions were similar to that exhibited by clinical inhibitors of XO (allopurinol, and febuxostat). This study identifies 5-aryl-1 H -tetrazoles as a new class of xanthine oxidase inhibitors, which deserves to be further, investigated for the treatment of hyperuricemia and gout. [ABSTRACT FROM AUTHOR]

The enzyme-mediated polymerization of bioactive phenolic compounds, such as the flavonoid rutin, has gained interest due to the enhanced physico-chemical and biological properties of the products, which increases their potential application as a nutraceutical. In this work, the influence of enzyme activity on rutin oligomerization was evaluated in reactions with low (1000 U/L) and high (10,000 U/L) initial laccase activities. For both reactions, high molecular weight oligomer fractions showed better properties compared to lower weight oligomers. Products of the reaction with low laccase activity exhibited thermal stability and antioxidant potential similar to control reaction, but led to higher inhibitory activity of xanthine oxidase and apparent aqueous solubility. Oligomers obtained in the reaction with high laccase activity showed better apparent aqueous solubility but decreased biological activities and stability. Their low antioxidant activity was correlated with a decreased phenolic content, which could be attributed to the formation of several bonds between rutin molecules. [ABSTRACT FROM AUTHOR]

Rhododendron tomentosum ( Ledum palustre ) is a bog shrub used in traditional medicine for treatment of respiratory and rheumatic diseases. Due to the large variability of the chemical composition of its essential oil, depending on the habitat, the in vitro cultures were established as the alternative source of the volatile fraction. There is a need to monitor a quality of the field grown as well as in vitro plant material, especially if potentially toxic aromadendrane derivatives are concerned. In this study the HPTLC method was developed and validated for quantification of ledol and alloaromadendrene in R. tomentosum essential oils obtained from the plants collected in various locations as well as in vitro cultures. For qualitative analysis, chromatograms were developed on HPTLC Si 60 plates at distance of 50 mm without preconditioning using hexane: ethyl acetate (9:1) and visualized with p -anisaldehyde reagent. For quantitative analysis, chromatograms were developed on HPTLC Si 60 plates at distance of 40 mm with 20 min preconditioning using hexane: ethyl acetate (9:1), visualized with vanillin/phosphoric acid reagent and subjected to densitometric detection (560 nm). The content of ledol and alloaromadendrene in different samples was determined using the validated HPTLC method (12–280 mg and 2–60 mg 100 g −1 dried plant material, respectively) and was compared with GC/MS results. The bioautographic antioxidant HPTLC assays in DPPH and in riboflavin-light-NBT systems as well as the test for xanthine oxidase inhibition were employed for screening of the biological activity of the R. tomentosum essential oils. [ABSTRACT FROM AUTHOR]

Gnaphalium affine D. Don, a medicinal and edible plant, has been used to treat gout in traditional Chinese medicine and popularly consumed in China for a long time. A detailed phytochemical investigation on the aerial part of G. affine led to the isolation of two new esters of caffeoylquinic acid named (−) ethyl 1, 4-di- O -caffeoylquinate ( 1 ) and (−) methyl 1, 4-di- O -caffeoylquinate ( 2 ), together with 35 known compounds ( 3 − 37) . Their structures were elucidated by spectroscopic data and first-order multiplet analysis. All the isolated compounds were tested for their xanthine oxidase inhibitory activity with an in vitro enzyme inhibitory screening assay. Among the tested compounds, 1 (IC 50 11.94 μmol·L −1 ) and 2 (IC 50 15.04 μmol·L −1 ) showed a good inhibitory activity. The current results supported the medical use of the plant. [ABSTRACT FROM AUTHOR]

Gout is a type of arthritis that causes painful inflammation in one or more joints. In gout, elevation of uric acid in the blood triggers the formation of crystals, causing joint pain. Malaysia is a mega-biodiversity country that is rich in medicinal plants species. Therefore, its flora might offer promising therapies for gout. This article aims to systematically review the anti-gout potential of Malaysian medicinal plants. Articles on gout published from2000 to 2017 were identified using PubMed, Scopus, ScienceDirect, and Google Scholar with the following keyword search terms: "gout," "medicinal plants," "Malaysia," "epidemiology," "in vitro," and "in vivo." In this study, 85 plants were identified as possessing anti-gout activity. These plants had higher percentages of xanthine oxidase inhibitory activity (>85%); specifically, the Momordica charantia, Chrysanthemum indicum, Cinnamomum cassia, Kaempferia galanga, Artemisia vulgaris, and Morinda elliptica had the highest values, due to their diverse natural bioactive compounds, which include flavonoids, phenolics, tannin, coumarins, luteolin, and apigenin. This review summarizes the anti-gout potential of Malaysian medicinal plants but the mechanisms, active compounds, pharmacokinetics, bioavailability, and safety of the plants still remain to be elucidated. [ABSTRACT FROM AUTHOR]

• Synthesis of pyrazole-benzamide-benzothiazole conjugates via hand grinding process. • In vitro xanthine oxidase inhibition analysis of title compounds (6a-j). • Evaluation of in vitro antioxidant property by DPPH, ABTS, and superoxide assays. • Docking simulation studies were performed. A series of benzothiazole bearing pyrazole derivatives (6a-j) were synthesized via mechanochemical synthesis through hand grinding using pestle and mortar, and their xanthine oxidase inhibition efficiency and antioxidant properties were evaluated. The 1H NMR, 13C NMR, FT-IR, and mass spectroscopy techniques were employed for the characterization of the synthesized molecules. Initially, the xanthine oxidase (XO) enzyme inhibitory activity for all the compounds (6a-j) was performed using standard reference. Further, for the potent compound (6h) with methyl sulphonyl substitution in the benzothiazole ring the kinetic analysis of XO was carried out. Later, anti-oxidant assays like DPPH, ABTS, and superoxide radical scavenging assays for title compounds were conducted. Also in these assays, the compound (6h) was found to exhibit good antioxidant activity, and the inhibitory constant of XO was found to be 1.78 µg. Furthermore, the docking and dynamic studies were carried out, and the compound (6h) was found to show the lowest binding energy. Also, the analysis of RMSD, RMSF, Rg, SASA, and the number of hydrogen bonds of the compound (6h) was conducted and the binding free energy of the compound (6h) was calculated. [Display omitted] [ABSTRACT FROM AUTHOR]

Barbituric and thiobarbituric acid derivatives have become progressively attractive to medicinal chemists due to their wide range of biological activities. Herein, different series of 1,3,5-trisubstituted barbiturates and thiobarbiturates were prepared in moderate to excellent yields and their activity as xanthine oxidase inhibitors, antioxidants, antibacterial agents and as anti-proliferative compounds was evaluated in vitro . Interesting bioactive barbiturates were found namely, 1,3-dimethyl-5-[1-(2-phenylhydrazinyl)ethylidene]pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione ( 6c ) and 1,3-dimethyl-5-[1-[2-(4-nitrophenyl)hydrazinyl]ethylidene]pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione ( 6e ), which showed concomitant xanthine oxidase inhibitory effect (IC 50 values of 24.3 and 27.9 μM, respectively), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (IC 50 values of 18.8 and 23.8 μM, respectively). In addition, 5-[1-(2-phenylhydrazinyl)ethylidene]pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione ( 6d ) also revealed DPPH radical scavenger effect, with an IC 50 value of 20.4 μM. Moreover, relevant cytotoxicity against MCF-7 cells (IC 50 = 13.3 μM) was observed with 5-[[(2-chloro-4-nitrophenyl)amino]methylene]-2-thioxodihydropyrimidine-4,6(1 H ,5 H )-dione ( 7d ). Finally, different 5-hydrazinylethylidenepyrimidines revealed antibacterial activity against Acinetobacter baumannii (MIC values between 12.5 and 25.0 μM) which paves the way for developing new treatments for infections caused by this Gram-negative coccobacillus bacterium, known to be an opportunistic pathogen in humans with high relevance in multidrug-resistant nosocomial infections. The most promising bioactive barbiturates were studied in silico with emphasis on compliance with the Lipinski's rule of five as well as several pharmacokinetics and toxicity parameters. [ABSTRACT FROM AUTHOR]

Xanthine oxidase (XO), an enzyme widely distributed among mammalian tissues, is associated with the oxidation of xanthine and hypoxanthine to form uric acid. Reactive oxygen species are also released during this process, leading to oxidative damages and to the pathology called gout. Available treatments mainly based on allopurinol cause serious side effects. Natural products such as flavonoids may represent an alternative. Thus, a series of polymethoxyflavones isolated and hemisynthesized from the bud exudates of Gardenia oudiepe has been evaluated for in vitro XO inhibitory activity. Compounds 1 , 2 and 3 were more active than the reference inhibitor, Allopurinol (IC 50 = 0.25 ± 0.004 μM) with IC 50 values of (0.004 ± 0.001) μM, (0.05 ± 0.01) μM and (0.09 ± 0.003) μM, respectively. Structure-activity relationships were established. Additionally, a molecular docking study using MOE™ tool was carried out to establish the binding mode of the most active flavones with the enzyme, showing important interactions with its catalytic residues. These promising results, suggest the use of these compounds as potential leads for the design and development of novel XO inhibitors. [ABSTRACT FROM AUTHOR]

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2,1-Benzisoxazoles, also called anthranils, are one of the two types of aromatic bicyclic heterocycles having a benzene ring fused with an isoxazole, which are particularly recognized as valuable intermediates in organic synthesis. Nevertheless several methods can be found in the literature to prepare 2,1-benzisoxazoles, we herein report a new, efficient, simple, mild, and alternative procedure to prepare 3-substituted-2,1-benzisoxazoles from 5-(2-nitrobenzylidene)barbiturates in moderate to good yields (51–82%). All the novel benzisoxazoles showed spectral data fully consistent with the assigned structures, which were unequivocally confirmed by single crystal X-ray analysis. A possible mechanism of the reaction is proposed. In addition, a screening of the bioactivity of these benzisoxazoles as xanthine oxidase inhibitors, antioxidants, and cytotoxic compounds was performed. The benzisoxazole formed from barbituric acid revealed moderate xanthine oxidase inhibitory effects (IC 50 = 22.10 μM). [ABSTRACT FROM AUTHOR]