Xanthine oxidoreductase inhibition – A review of computational aspect

2020 ◽  
Vol 19 (04) ◽  
pp. 2040008
Author(s):  
Chao Dong ◽  
Milka Montes ◽  
Wael M. Al-Sawai
Keyword(s):  
Uric Acid ◽  
Quantum Mechanics ◽  
Xanthine Oxidase ◽  
Molecular Mechanics ◽  
Computational Methods ◽  
Computational Aspect ◽  
Xanthine Oxidoreductase ◽  
Oxidase Inhibition ◽  
Xanthine Oxidase Inhibition ◽  
Inhibition Studies

Xanthine Oxidoreductase (XOR) exists in a variety of organisms from bacteria to humans and catalyzes the oxidation of hypoxanthine to xanthine and from xanthine to uric acid. Excessive uric acid could lead to gout and hyperuricemia. In this paper, we have reviewed the recent computational studies on xanthine oxidase inhibition. Computational methods, such as molecular dynamics (molecular mechanics), quantum mechanics, and quantum mechanics/molecular mechanics (QM/MM), have been employed to investigate the binding affinity of xanthine oxidase with synthesized and isolated nature inhibitors. The limitations of different computational methods for xanthine oxidase inhibition studies were also discussed. Implications of the computational approach could be used to help to understand the existing arguments on substrate/product orientation in xanthine oxidase inhibition, which allows designing new inhibitors with higher efficacy.

scholarly journals Xanthine oxidase inhibition in SARS-CoV-2 infection: the mechanism and potency of allopurinol and febuxostat in COVID-19 management

2020 ◽  
Author(s):  
Irandi Putra Pratomo ◽  
Anna Ariane ◽  
Aryo Tedjo ◽  
Rudi Heryanto ◽  
Rafika Indah Paramita
Keyword(s):  
Uric Acid ◽  
Severe Acute Respiratory Syndrome ◽  
Literature Review ◽  
Xanthine Oxidase ◽  
Curative Therapy ◽  
Definitive Therapy ◽  
The World ◽  
Oxidase Inhibition ◽  
Repurposed Drugs ◽  
Xanthine Oxidase Inhibition

The number of coronavirus disease 2019 (COVID-19) infection cases has been increasing globally, including in Indonesia. Definitive therapy for COVID-19 has not yet been found; hence, repurposed drugs for COVID-19 have been considered and have been practiced by several researchers in the world. This literature review investigates the action of xanthine oxidase as a component of the biomolecular pathway against severe acute respiratory syndrome-related coronavirus-2, the cause of COVID-19, and describes the mechanism and potential of uric acid drugs (allopurinol and febuxostat) as prophylaxis and curative therapy for COVID-19. 

scholarly journals The Potential for Xanthine Oxidase Inhibition in the Prevention and Treatment of Cardiovascular and Cerebrovascular Disease

2009 ◽  
Vol 2009 ◽  
pp. 1-9 ◽  
Author(s):  
Peter Higgins ◽  
Jesse Dawson ◽  
Matthew Walters
Keyword(s):  
Uric Acid ◽  
Xanthine Oxidase ◽  
Clinical Data ◽  
Large Scale ◽  
Cardiovascular Disorders ◽  
Clinical Endpoints ◽  
Prevention And Treatment ◽  
Oxidase Inhibition ◽  
Xanthine Oxidase Inhibition ◽  
Acid Reduction

There is a now a wealth of epidemiological, animal, and clinical data to suggest the benefits of uric acid reduction and xanthine oxidase inhibition in prevention of vascular disease. This review discusses the available epidemiological, preclinical, and clinical data and considers arguments for and against a role for serum uric acid in common cardiovascular disorders. It concludes that large scale trials with clinical endpoints are justified to address this important question and to define whether use of drugs such as allopurinol should be a routine part of preventative strategies.

scholarly journals Hypouricemic Activity of Pentopetia Androsaemifolia Decne. (Apocynaceae) Hydro Alcoholic Extract in Mice

2017 ◽  
Vol 13 (36) ◽  
pp. 340
Author(s):  
Randrianavony P. ◽  
Reboza A.M. ◽  
Quansah N. ◽  
Randimbivololona F.
Keyword(s):  
Uric Acid ◽  
Oral Administration ◽  
Xanthine Oxidase ◽  
Acid Concentration ◽  
Intraperitoneal Injection ◽  
Uric Acid Concentration ◽  
Alcoholic Extract ◽  
Oxidase Inhibition ◽  
Xanthine Oxidase Inhibition ◽  
Potassium Oxonate

The aim of this work was to investigate the uricemic and uricosuric activity of the hydro alcoholic extract of Pentopetia androsaemifolia in experimentally induced hyperuricemic mice. Hyperuricemia was induced in the mice by intraperitoneal injection of potassium oxonate. Oral administration of the extract at doses 50 to 200 mg/kg reduce hyperuricemia from 218.78 ± 7.50 to 72.29 ± 16.88 mg/l (P< 0. 05). The same doses of 50 to 200 mg/kg of the extract also reduce uricosuria from 125.4 ± 4.4 to 70 ± 12.6 mg/l (p< 0.05). A direct correlation exists between plasma uric acid concentration and urine uric acid concentration (r = 0.99). The hypouricemic activity of the extract could be due to xanthine oxidase inhibition by the flavonoids present in the extract.

scholarly journals Anti-Hyperuricemic and Uricosuric Potential of Berberis vulgaris in Oxonate-Induced Hyperuricemic Rats

Dose-Response ◽  
2021 ◽  
Vol 19 (3) ◽  
pp. 155932582110403
Author(s):  
Muhammad Bilal ◽  
Saeed Ahmad ◽  
Tayyeba Rehman ◽  
Aymen Owais Ghauri ◽  
Sana Khalid ◽  
...  
Keyword(s):  
Uric Acid ◽  
Xanthine Oxidase ◽  
Elevated Serum ◽  
Small Sample ◽  
Dependent Manner ◽  
Berberis Vulgaris ◽  
Oxidase Inhibition ◽  
Xanthine Oxidase Inhibition

Hyperuricemia is a metabolic disorder with characteristic elevated serum uric acid. Recently, several plant-based medicines are being used for the treatment of hyperuricemia. The study aimed to find the hypouricemic potential of Berberis vulgaris in in-vitro and in-vivo study models. In i n-vitro studies, xanthine oxidase inhibition assay was performed to evaluate IC50 value and capsule absorbance of the drug, respectively. For in-vivo experiment, the study comprised 15 groups of rats. In-vitro results revealed that significant xanthine oxidase inhibition was shown by Berberis vulgaris with an IC50 value of 272.73±.3 μg/mL. Similarly, oral administration of Berberis vulgaris with dosages of 250 and 500 mg/kg decreased serum and liver uric acid levels significantly in a dose- and time-dependent manner in oxonate-induced hyperuricemic rats. Furthermore, 3-day and 7-day administration of Berberis vulgaris showed more potential compared to 1-day administrations. The present study indicated marked hypouricemic effects of Berberis vulgaris in rats. Due to caveat of the small sample size, a firm assumption of the hypouricemic effect of Berberis vulgaris cannot be made. However, extensive study is needed to find out the exact molecular mechanism involved and to translate its effects into clinical trials for the further validation of the results.

The Pharmacokinetics of Injectable Allopurinol in Newborns With the Hypoplastic Left Heart Syndrome

PEDIATRICS ◽  
1994 ◽  
Vol 94 (6) ◽  
pp. 820-823 ◽  
Author(s):  
Susan Phillips McGaurn ◽  
Robert R. Clancy ◽  
Lisa E. Davis ◽  
Motria M. Krawczeniuk ◽  
John D. Murphy ◽  
...  
Keyword(s):  
Uric Acid ◽  
Xanthine Oxidase ◽  
Serum Uric Acid ◽  
Ischemia Reperfusion ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Elimination Half ◽  
Oxidase Inhibition ◽  
Xanthine Oxidase Inhibition ◽  
Left Heart Syndrome

Objective. The purpose of this investigation was to determine the pharmacokinetic disposition of intravenous allopurinol and its metabolite oxypurinol in neonates with the hypoplastic left heart syndrome (HLHS) and to evaluate the subsequent degree of xanthine oxidase inhibition using serum uric acid as a marker. Methods. Pharmacokinetic data were evaluated in 12 stable preoperative neonates with HLHS after a single intravenous allopurinol administration of 5 mg/kg or 10 mg/kg. Pharmacokinetic parameters were determined for elimination half-life, clearance, volume of distribution, and mean residence time. Xanthine oxidase inhibition, measured by serum uric acid reduction, was also measured. Results. Pharmacokinetic parameters revealed no statistically significant differences between a 5-mg/kg and 10-mg/kg dose of intravenous allopurinol on elimination half-life, clearance, volume of distribution, and mean residence time. Mean serum uric acid levels were significantly reduced from baseline by 39.99 and 42.94%, respectively, in the 5- and 10-mg/kg treatment groups. Discussion. The enzyme xanthine oxidase plays a key biochemical role in the generation of toxic oxygen-derived free radicals during ischemia-reperfusion conditions. Allopurinol and its active metabolite oxypurinol inhibit xanthine oxidase, and significantly reduce the conversion of hypoxanthine to xanthine and xanthine to uric acid. Cell injury may be caused by toxic oxygen free radicals produced by ischemia-reperfusion injury such as could occur during the repair of HLHS under hypothermic total circulatory arrest. We hypothesize that allopurinol may provide protection from cellular injury in this clinical context.

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