Xanthine Oxidase Research Articles

Discovery of 4-(isopentyloxy)-3-nitrobenzamide derivatives as xanthine oxidase inhibitors through a non-anthraquinone exploration.

In our previous study, we reported a series of N-(9,10-anthraquinone-2-carbonyl) amino acid derivatives as novel inhibitors of xanthine oxidase (XO). Recognizing the suboptimal drug-like properties associated with the anthraquinone moiety, we embarked on a nonanthraquinone medicinal chemistry exploration in the current investigation. Through systematic structure-activity relationship (SAR) studies, we identified a series of 4-(isopentyloxy)-3-nitrobenzamide derivatives exhibiting excellent in vitro potency against XO. The optimized compound, 4-isopentyloxy-N-(1H-pyrazol-3-yl)-3-nitrobenzamide (6k), demonstrated exceptional in vitro potency with an IC50 value of 0.13 μM. Compound 6k showed favorable drug-like characteristics with ligand efficiency (LE) and lipophilic ligand efficiency (LLE) values of 0.41 and 3.73, respectively. In comparison to the initial compound 1d, 6k exhibited a substantial 24-fold improvement in IC50, along with a 1.6-fold enhancement in LE and a 3.7-fold increase in LLE. Molecular modeling studies provided insights into the strong interactions of 6k with critical amino acid residues within the active site. Furthermore, in vivo hypouricemic investigations convincingly demonstrated that 6k significantly reduced serum uric acid levels in rats. The MTT results revealed that compound 6k is nontoxic to healthy cells. The gastric and intestinal stability assay demonstrated that compound 6k exhibits good stability in the gastric and intestinal environments. In conclusion, compound 6k emerges as a promising lead compound, showcasing both exceptional in vitro potency and favorable drug-like characteristics, thereby warranting further exploration.

Purification, characterization and anti-hyperuricemic mechanism of novel xanthine oxidase inhibitory peptides from tea (Camellia sinensis L.) protein

In this study, two novel xanthine oxidase inhibitory peptides, PDEAVAYG (820.3602 Da) and IAAGLQNTG (843.4450 Da), were purified and identified from tea protein hydrolysate, and their IC50 values were 0.09 mg/mL (109.71 μM) and 0.24 mg/mL (284.55 μM), respectively. During the gastrointestinal simulation digestion, PDEAVAYG was broken down into new peptides, while IAAGLQNTG exhibited some stability. Molecular docking results showed that hydrogen bonding, π-π stacking, and hydrophobic interactions exerted crucial effects on the interaction between peptides and xanthine oxidase. In the hyperuricemia cell model, compared to the model group, 1.0 mg/mL of PDEAVAYG and IAAGLQNTG decreased cellular uric acid levels by 40.80% and 33.33%, respectively. The RNA-seq experiments revealed that PDEAVAYG could alleviate hyperuricemia by regulating mRNA expression for pro-inflammatory factors, growth factors associated with cardiovascular disease, and uric acid efflux transporter proteins in cells. This study provides a new theoretical reference for the development of functional foods or nutritional supplements using peptides with anti-hyperuricemic activity.

Xanthine Oxidase in Rats, Mice, and Humans with Polycystic Kidney Disease

Xanthine Oxidase in Rats, Mice, and Humans with Polycystic Kidney Disease

Preparing Ganoderma lucidum slices by improved steam explosion enhances their apparent, functional and structural properties

Ganoderma lucidum slices exhibit antioxidant and enzyme inhibitory activity, enhancing vitality and longevity. However, untreated Ganoderma lucidum slices fail to meet specific physical and chemical requirements for consumption and processing because their bioactive compounds must be released before intake through effective pretreatment. We proposed developing a novel preparation method for Ganoderma lucidum slices through improved steam explosion (ISE). The effect of ISE (at 0.4–1.2 MPa for 5 min) on their chemical compounds, apparent properties, biological activity, sensory quality and structural characteristics was assessed. The results showed that ISE (0.8–1.2 MPa) increased the content of flavonoids (by 32.29 %–126.57 %), phenolics (by 31.79 %–96.28 %), triterpenes (by 1.74–5.24 times) and polysaccharides (by 6.27–18.03 times) in Ganoderma lucidum slices. Additionally, ISE improved the color saturation and hue of their infusions while reducing the color values of these slices. Under all conditions, ISE significantly increased the soluble solids content (by 1.31–11.44 times) and the inhibitory activity of tyrosinase and xanthine oxidase when compared to infusions of untreated slices. At 0.8–1.2 MPa, the radical scavenging activity of 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) was also significantly higher in steam-exploded slices than in untreated slices. In the sensory evaluation, steam-exploded slices outperformed untreated slices in terms of color, taste, form attributes, and overall score. ISE disrupted the microstructure of Ganoderma lucidum slices, whose microscopic structure was broken into fragments, thereby promoting the dissolution of bioactive compounds and enhancing their biological functions, as shown in this study. Therefore, ISE improved the nutritional and medicinal effects of the fruiting body of Ganoderma lucidum by facilitating nutritional retention and resource utilization efficiency.

Cardiovascular Outcomes of Uric Acid Lowering Medications: A Meta-Analysis.

Although hyperuricemia is a recognized risk factor for cardiovascular diseases, mixed results have been reported regarding the associations between uric acid-lowering medications and cardiovascular events. This meta-analysis compared the cardiovascular outcomes of different uric acid-lowering medications and placebo. Following PRISMA guidelines, we searched OVID Medline, Embase, Web of Science, and Cochrane databases to identify potentially relevant articles until December 2023. Studies must be randomized or observational, report cardiovascular and mortality outcomes, and compare uric acid-lowering medications to placebo or each other. Data was analyzed using Revman (version 5.4) software. A total of 3,393 studies were searched, after which 47 studies were included, totaling 3,803,509 patients (28 studies comparing xanthine oxidase inhibitors (XOI) versus placebo, 17 studies comparing allopurinol and febuxostat, and 2 studies comparing XOI and uricosuric agents). Overall mean age was 57.3years, and females comprised 20.8% of all studies. There were no significant differences between XOI and placebo for cardiovascular outcomes (mortality, myocardial infarction, major adverse cardiovascular events, heart failure, or arrhythmia). There was significant heterogeneity in all these pooled analyses. Comparing Allopurinol to Febuxostat, there was a lower risk of heart failure in febuxostat than allopurinol in 3 RCTs (OR 0.66, 95% CI 0.50-0.89, p = 0.006). Other cardiovascular outcomes were not different. Lastly, when comparing XOI and uricosuric agents, no significant differences in MI rates were evident. XOI was not associated with reduced cardiovascular events compared to placebo. When comparing XOI agents, Febuxostat might reduce the risk of HF, but future studies are required to confirm the findings from the current study.

Integrating metabolomics with network pharmacology to reveal the mechanism of Poria cocos in hyperuricemia treatment

Ethnopharmacological relevanceHyperuricemia is a chronic condition characterized by persistently elevated uric acid levels, often leading to gouty arthritis and renal insufficiency. Poria cocos F.A.Wolf, a traditional Chinese medicinal herb, possesses notable diuretic and anti-inflammatory properties and is widely used to treat edema, inflammation, viral infections, and tumors. Recent studies suggest that Poria cocos has the potential to lower uric acid levels and mitigate kidney damage, making it a promising candidate for hyperuricemia treatment. However, its pharmacological mechanisms require further exploration. Aim of the studyThis study aims to elucidate the mechanisms by which Poria cocos alleviates hyperuricemia, using metabolomics and network pharmacology approaches. Materials and methodsHyperuricemia was induced in rats via a high-yeast diet combined with potassium oxonate. The effects of Poria cocos were assessed by measuring serum uric acid, creatinine, urea nitrogen levels, hepatic xanthine oxidase activity, and renal tissue morphology. Non-targeted metabolomics was employed to identify differential metabolites and explore the metabolic pathways involved in its therapeutic effects. Network pharmacology was utilized to analyze potential targets and signaling pathways, which were validated through molecular docking and ELISA analysis. ResultsPoria cocos extract significantly reduced serum uric acid, creatinine, and urea nitrogen levels, inhibited xanthine oxidase activity, and attenuated kidney damage. Metabolomics combined with network pharmacology identified xanthine dehydrogenase and fatty acid synthase as key targets, while purine metabolism, fatty acid biosynthesis, and primary bile acid biosynthesis were identified as critical pathways. ELISA confirmed that Poria cocos suppressed xanthine dehydrogenase and fatty acid synthase expression in hyperuricemic rats. Molecular docking further verified strong binding interactions between core compounds and key targets. ConclusionsPoria cocos alleviates hyperuricemia by modulating multiple compounds, targets, and pathways. Through network pharmacology and metabolomics, it reveals that Poria cocos selectively regulates xanthine dehydrogenase and fatty acid synthase, influencing purine metabolism, fatty acid biosynthesis, and primary bile acid biosynthesis pathways. These findings provide insights into its therapeutic mechanisms, supporting the clinical application of Poria cocos in treating metabolic disorders and kidney damage associated with hyperuricemia.

Insights into the modulatory effects of host-gut microbial xanthine co-metabolism on high-fat diet-fed mice.

Gut microbiota-mediated endobiotic and xenobiotic metabolism play crucial roles in disease progression, and drug therapy/toxicity. Our recent study suggested that gut microbiota-mediated xanthine metabolism is correlated with resistance to high-fat diet (HFD)-induced obesity. Here, we explored the role of host-gut microbial xanthine co-metabolism in the prevention and treatment of HFD-induced obesity by orally administration of Bifidobacterium longum, xanthine, and a xanthine oxidase inhibitor (topiroxostat). The findings indicate that xanthine exhibits a significantly protective effect against HFD-induced obesity. While B. longum, xanthine, and topiroxostat did not alleviate the dysbiosis of the weight and glucose metabolism of HFD-induced obesity (DIO) and obesity resistance (DIR) mice. 16S rRNA sequencing analyses revealed that treatments with B. longum significantly altered gut microbiota composition in HFD-fed and DIO mice. Microbial interaction network analysis revealed several Bacteroidetes species, such as Amulumruptor caecigallinarius and Muribaculum intestinale, as keystone taxa that were notably enriched by B. longum. Untargeted metabolomics analysis implied that xanthine might serve as a crucial molecule in regulating body weight, exerting a preventive effect on HFD-induced obesity. This study offers new perspectives on the influence of host-gut microbial xanthine co-metabolism on HFD-fed mice and emphasizes the promising role of xanthine in promoting weight loss.

Bioactivity-guided purification and characterization of antioxidant, anti-gout and anti-diabetic polyphenols from Panchkuta: A traditional food combination of (semi) arid regions

Desert ecosystems have thrived in part because of the contribution of local traditions, along with conventional knowledge passed down through generations. Panchkuta, a combination of five plants, including Prosopis cineraria, Cordia dichotoma, Capparis decidua, Acacia senegal, and Mangifera indica, is a classic example of ethnic desert food and how communities utilize existing food resources to ensure nutritional security. In this study, we determined the total phenolic content, total flavonoid content, antioxidant, anti-gout, and anti-diabetic activities of crude and purified (using Amberlite XAD7HP and Sephadex LH-20) fractions of Panchkuta. Further, the phenolic compounds (quercetin, tiliroside, myricetin-3-O-galactoside, and others) responsible for these activities were identified by analytical techniques, including TLC, LC-MS, and HR-MS. The purified fraction showing maximum antioxidant activity in DPPH assay (Fraction 16, IC50–156.65 ± 12.6 μg/ml) was validated for its cytoprotective and anti-lipid peroxidative effects in the in vitro cell culture system (murine fibroblast cells). Fraction 9 showed the maximum anti-gout activity in xanthine oxidase assay (IC50- 80.59 ± 9.89 μg/ml) and fraction 11 showed the maximum anti-diabetic activity in α-amylase assay (IC50 of 101.54 ± 14.7 μg/ml). The study reinforces the understanding of traditional knowledge, relevance to One Health, and authenticates the potential medicinal value of Panchkuta through scientific validation.

Integrated microbiome and metabolome analysis reveals the key role of taurohyocholate in the treatment of hyperuricemia with Lacticaseibacillus rhamnosus 2016SWU.05.0601

The incidence of hyperuricemia (HUA) is on the rise, posing a significant threat to human health. Several probiotics have shown potential in treating HUA; however, the critical role of intestinal metabolites in this therapy remains inadequately understood. Our study demonstrated that Lacticaseibacillus rhamnosus 2016SWU.05.0601 not only reduced the expression levels of xanthine dehydrogenase and the content and activity of xanthine oxidase in the liver but also regulated the uric acid transporters expression in the kidney, thereby attenuating HUA in mice. Additionally, L. rhamnosus 2016SWU.05.0601 modulated the gut microbiota and metabolite abundance in HUA mice. Correlation analysis revealed that the gut microbiota metabolite taurohyocholate played a vital role in the treatment of HUA by L. rhamnosus 2016SWU.05.0601, as confirmed in HUA cell models. Our research provides a significant theoretical basis for elucidating the mechanisms by which probiotics alleviate HUA and for developing functional ingredients for HUA treatment.

Antidiabetic and Antigout Properties of the Ultrasound-Assisted Extraction of Total Biflavonoids from Selaginella doederleinii Revealed by In Vitro and In Silico Studies.

In this study, the extraction, purification and metabolic enzyme inhibition potential of Selaginella doederleinii were investigated. In order to extract the total biflavonoids from S. doederleinii (SDTBs), the optimum extraction process was obtained by optimizing the ultrasonic extraction parameters using response-surface methodology. This resulted in a total biflavonoid content of 22.26 ± 0.35 mg/g. Purification of the S. doederleinii extract was carried out using octadecylsilane (ODS), and the transfer rate of the SDTBs was 82.12 ± 3.48% under the optimum purification conditions. We determined the effect of the SDTBs on α-glucosidase (AG), α-amylase and xanthine oxidase (XOD) and found that the SDTBs had an extremely potent inhibitory effect on AG, with an IC50 value of 57.46 μg/mL, which was much lower than that of the positive control. Meanwhile, they also showed significant inhibition of XOD and α-amylase, with IC50 values of 289.67 μg/mL and 50.85 μg/mL, respectively. In addition, molecular docking studies were carried out to understand the nature of the action of the biflavonoids on AG and XOD. The results showed that robustaflavone had the lowest binding energy to AG (-11.33 kcal/mol) and XOD (-10.21 kcal/mol), while, on the other hand, amentoflavone showed a good binding affinity to AG (-10.40 kcal/mol) and XOD (-9.962 kcal/mol). Moreover, molecular dynamics simulations verified the above results.

Rapid screening of xanthine oxidase inhibitors from Ligusticum wallichii by using xanthine oxidase functionalized magnetic metal-organic framework.

In this study, xanthine oxidase was immobilized for the first time using a novel magnetic metal-organic framework material (Fe3O4-SiO2-NH2@MnO2@ZIF-8-NH2). A ligand fishing method was established to rapidly screen XOD inhibitors from Ligusticum wallichii based on the immobilized XOD. Characterization and properties of the immobilized enzyme revealed its excellent stability and reusability. A ligand was screened from Ligusticum wallichii and identified as ligustilide by ultra-high performance liquid chromatography tandem mass spectrometry. The IC50 value of ligustilide was determined to be 27.70 ± 0.13μM through in vitro inhibition testing. Furthermore, molecular docking verified that ligustilide could bind to amino acid residues at the active site of XOD. This study provides a rapid and effective method for thepreliminary screening of XOD inhibitors from complex natural products and has great potential for further discovery of anti-hyperuricemic compounds.

Antioxidant and Xanthine oxidase inhibitory activities of the tea (Camellia sinensis) flower

The major purpose of this study was to investigate the DPPH radical scavenging activity, hydroxyl radical scavenging activity, superoxide radical scavenging activity, reducing power, ferrous ion chelating activity, and xanthine oxidase activity for research of antioxidant and xanthine oxidase inhibitory activities using a variety of extracts of tea (Camellia sinensis) flower. Among the several extracts, when 800 μg/mL of the ethanol extract was used, the maximum DPPH radical scavenging activity was obtained, 79.2%, which was approximately 80.8% compared to L-ascorbic acid, the maximum hydroxyl radical scavenging activity, 71.3%, which was approximately 73.2% compared to BHA, and the maximum super oxide radical scavenging activity, 89.4%, which was, approximately 90.6% compared to BHT, and the maximum reducing power, 1.94 at an OD of 700 nm, which was approximately 49.2% compared to L-ascorbic acid, respectively. On the other hand, when 800 μg/mL of the hot water extract was used, the maximum activity of ferrous ion chelate was obtained, 28.6%, which was approximately 48.4% compared to EDTA and the maximum xanthine oxidase inhibitory activity, 61.4%, approximately 63.8% compared to catechin, respectively. These results indicated the application potential for industries that can produce new biomaterials that can compensate for the shortcomings of existing synthetic antioxidants and use discarded tea flower as food, pharmaceutical, and cosmetic materials.

Glutaredoxin-1 and Others Antioxidants Enzymes in Two Subtypes (B-cell and T-cell) of Acute Lymphoblastic Leukemia Patients

The 5-year event-free viability for acute lymphoblastic leukemia (ALL) have enhanced in many study groups due to modern paediatric clinical trials, however T-cell ALL results are still lagging by 5–10% in most studies. The goal of this study was to measure the Glutaredoxin-1(Grx1) as an antioxidant, and also to measure each of the methionine sulfoxide reductaseA(MsrA),myeloperoxidase(MPO), catalase(CAT), xanthine oxidase(XO), glutathione (GSH), albumin (Alb), and complete blood counts (CBC) in two subtypes (B-cell and T-cell) of ALL patients compared with control group between the ages of two and fifteen years. Revealed with the results of this study, Grx1, CAT, MDA levels increased statistically significantly in two subtypes of acute lymphocytic leukemia Patients compared with control group, but MsrA, GSH, Alb, and CBC levels declined considerably in two subtypes for patients compared with control group. Finally MPO have non-significant difference in compared.The study concluded that there was a high increase in the level of Grx1, which participates in rescuing blood components from the process of breakdown in which a decrease was observed n for two subtypes (B-cell and T-cell), in addition to a decrease in MsrA, GSH, which works to repair the damage occurring in the proteins of cell components, including blood components, malignant B cells are particularly sensitive in contrast to the T cell.

Bis-Chalcones: Recent Reports of Their Diverse Applications in Biological and Material Sciences.

Originating from the basic chalcone structure, bis-chalcones are characterized by their dual α,β-unsaturated carbonyl systems and carry a range of biological activities that include antimicrobial, antiviral, antiparasitic, antioxidant, antiproliferative, and chemical reactivities that warrant a review to cover recent progress. Thus, this review presents the significant potential demonstrated by bis-chalcones in various biological applications. For example, compounds 2.3.1 showed excellent antiparasitic activity against leishmania with good selectivity index, and compounds 2.2.1-2.2.3 showed submicromolar activity against SupT1 cells. Compound 2.6.22 stood out in its antiproliferative activity against a panel of 60 different cell lines. Compounds 2.6.4 and 2.6.9 have been shown as submicromolar noncompetitive xanthine oxidase inhibitors. We also present their recent applications in material science, for example, as photosensitizers and photoinitiators, to showcase their broader potential for innovation in both medicinal chemistry and industrial applications.

Interaction of Tri-Cyclic Nucleobase Analogs with Enzymes of Purine Metabolism: Xanthine Oxidase and Purine Nucleoside Phosphorylase.

Fluorescent markers play important roles in spectroscopic and microscopic research techniques and are broadly used in basic and applied sciences. We have obtained markers with fluorescent properties, two etheno derivatives of 2-aminopurine, as follows: 1,N2-etheno-2-aminopurine (1,N2-ε2APu, I) and N2,3-etheno-2-aminopurine (N2,3-ε2APu, II). In the present paper, we investigate their interaction with two key enzymes of purine metabolism, purine nucleoside phosphorylase (PNP), and xanthine oxidase (XO), using diffraction of X-rays on protein crystals, isothermal titration calorimetry, and fluorescence spectroscopy. Crystals were obtained and structures were solved for WT PNP and D204N-PNP mutant in a complex with N2,3-ε2APu (II). In the case of WT PNP-1,N2-ε2APu (I) complex, the electron density corresponding to the ligand could not be identified in the active site. Small electron density bobbles may indicate that the ligand binds to the active site of a small number of molecules. On the basis of spectroscopic studies in solution, we found that, in contrast to PNP, 1,N2-ε2APu (I) is the ligand with better affinity to XO. Enzymatic oxidation of (I) leads to a marked increase in fluorescence near 400 nm. Hence, we have developed a new method to determine XO activity in biological material, particularly suitable for milk analysis.

Design, synthesis, and evaluation of chalcone derivatives as xanthine oxidase inhibitors

Xanthine oxidase (XO) is an important enzyme that catalyzes the oxidation of hypoxanthine to xanthine and xanthine to uric acid in the catabolism of purines in humans. This makes XO a well-recognized target in alleviating hyperuricemia. The present study adapted a structure-based drug discovery approach to develop potent and low-toxicity XO inhibitors with the chalcone skeleton. We introduced a carboxyl group and a hydroxyl group to the B ring and modified the A ring. 35 chalcone derivatives were designed and synthesized. All the 35 derivatives exhibited higher XO inhibition activities (IC50=0.064-0.559μM) compared with allopurinol (IC50=2.588μM). Their high affinity was attributed to strong hydrogen bond interactions formed between the introduced carboxyl and hydroxyl groups with key amino acid residues in XO. SAR analysis disclosed that carboxyl, hydroxyl, ethyl (12c), methylamino (12h), dimethylamino (12i), indolin (13k), and indol (13l) groups played important roles in improving the whole molecules' inhibition potency against XO. ADME predictions and cytotoxicity assays suggested their pharmacokinetic characteristics and biocompatibility were desirable. Additionally, 12c exhibited a significant hypouricemic effect on potassium oxonate-induced hyperuricemia rats after orally administrated at a dose range of 10-40mg/kg, representing a promising anti-hyperuricemia potential for further optimization and development.

Chemical profile and biological activities of Lysiphyllum binatum (Blanco) de Wit.

Lysiphyllum binatum (Blanco) de Wit in the Fabaceae family, despite its traditional medicinal uses, has not been the subject of prior scientific inquiry into its chemical and biological profile. The dichloromethane and MeOH extracts of its roots exhibited notably similar antioxidant activity, while the dichloromethane extract of the vine stems showed aromatase inhibition. This study aimed to identify the bioactive components responsible for these activities. Chemical investigation of the roots led to the isolation of six new metabolites, named lysiphans A-F (1-6), along with eight known compounds (7-14). The vine stem yielded lysiphan C (3) and compound 7, as well as five known isolates (15-19). The structures of these metabolites were determined through NMR spectral analysis, HRESIMS, quantum chemical calculations of NMR and ECD spectra, and Mosher's modifications to establish their absolute configurations. The biogenetic relationships between the new compounds were proposed. Several of the isolates were evaluated for their antioxidant, anti-aromatase, and cytotoxic properties. Lysiphan B (2) exhibited significant antioxidant activity, with an IC50 value of 28.8 ± 0.4μM in the diphenyl picrylhydrazyl radical (DPPH) assay, 3.5 ± 0.2μM in the xanthine/xanthine oxidase (XXO) assay, and 1.5 ± 0.0 ORAC units in oxygen radical absorbance capacity (ORAC) assay. Additionally, compounds 12, 13, and 16 exhibited very strong aromatase inhibitory activity with IC50 values of 0.3 ± 0.2, 4.7 ± 0.1, and 0.9 ± 0.2µM, respectively. Compound 16 also demonstrated strong ORAC activity of 1.9 ± 0.1 ORAC units.

Synthesis and Structure-Activity Relationship Analysis of 2-Substituted-1,2,4-Triazolo[1,5-a]Pyrimidin-7-Ones and their 6-Carboxylate Derivatives as Xanthine Oxidase Inhibitors.

Hyperuricemia is characterised by high blood levels of uric acid, and it can degenerate into gout when monosodium urate crystals precipitate in joints and other tissues. Uric acid is produced during the catabolism of xanthine by the enzyme xanthine oxidase (XO), which is the primary therapeutic target in gout treatment. Current XO inhibitors approved to treat gout, such as allopurinol and febuxostat, suffer from serious adverse effects, creating the need for new drug molecules. Three libraries comprising 75 purine analogues were designed using a 1,2,4-triazolo[1,5-a]pyrimidine scaffold, synthesised and tested in vitro as potential XO inhibitors. The screening identified that 23 compounds exhibited better inhibitory activity than allopurinol, with 2-(4-isopropoxyphenyl)-7-oxo-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine-6-carboxylic acid being 23 times more potent. Enzyme kinetics studies and molecular docking simulations were performed on the most active compounds to identify the mechanism of action and intermolecular interactions between the active site of XO and the inhibitors. The most potent compounds exhibited a mix-type inhibition mechanism and were predicted to interact with the same amino acid residues as allopurinol. These novel purine analogues are promising hits for further new lead development among purine-like drug XO inhibitors with therapeutic potential in the treatment of hyperuricemia and associated diseases.

Insights into the biocompatibility of biodegradable metallic molybdenum for cardiovascular applications-a critical review.

Atherosclerotic cardiovascular disease (ACD) is the leading cause of death worldwide. The gold standard of treatment is the implantation of a permanent stent implant that is often associated with complications such as thrombus formation, vascular neointimal response, and stent fracture, which altogether decrease the long-term safety and efficacy of the stent. Biodegradable metallic materials have become an attractive alternative because of the ability to facilitate a more physiological healing response while the metal degrades. Recently, Molybdenum (Mo) has been considered as a potential candidate due to its excellent mechanical and medical imaging properties. Moreover, the biomedical research studies performed to date have shown minimal adverse effects in vitro and in vivo. However, there are still concerns of toxicity at high doses, and the impact of the biochemical mechanisms of Mo on material performance especially in pathophysiological environments are yet to be explored. Mo is an essential co factor for enzymes such as xanthine oxidoreductase (XOR) that plays a critical role in vascular homeostasis and ACD progression. Herein, this review will focus on the biochemistry of Mo, its physiological and pathological effects with an emphasis on cardiovascular disease as well as the recent studies on Mo for cardiovascular applications and its advantages over other biodegradable metals. The limitations of Mo research studies will also be discussed and concluded with an outlook to move this revolutionary metallic biomaterial from the bench to the bedside.

Phytochemical contents and antioxidant activity Paliurus spina-christi Miller leaf and seed extracts: PASS predictions, in silico studies on xanthine oxidase and cytochrome P450 1A1

Paliurus spina-christi Miller (PSC) is a shrub plant with important biological activities. For this reason, the phytochemical and biological activities of the PSC leaf and seed extracts were investigated in our study. This study performs phytochemical analyses (total phenol and flavonoid content, LC-ESI-MS/MS, and GC-MS/MS) and bioactivity assays (antioxidant) for the PSC leaves and seeds. In silico study and PASS prediction of main compounds in LC-ESI-MS/MS and GC-MS/MS analysis were also investigated. The leaf extract showed a high total phenolic and flavonoid content. In addition, the contents of hesperidin (25.548 mg/g extract) were high in the LC-ESI-MS/MS and GC-MS/MS analyses. It was noted that the leaf extract's antioxidant activities were higher than standard. The molecular docking of hesperidin with xanthine oxidase and cytochrome P450 1A1 had high MolDock score (-179.68, -149.156) and binding energy (-11.40 kcal/mol, -9.90 kcal/mol), respectively. This investigation pioneered using PSC leaf extracts as food supplements and medicine.