• Thu. Sep 21st, 2023

It seems that the inhibitory activity of the compounds depends on the position of the hydroxyl group (4a equatorial, 4b axial) at the glycoside substituting the hydroxyl group C3 of the basic flavonoid structure (Fig


May 29, 2023

It seems that the inhibitory activity of the compounds depends on the position of the hydroxyl group (4a equatorial, 4b axial) at the glycoside substituting the hydroxyl group C3 of the basic flavonoid structure (Fig. legume plant extracts are novel, natural XO inhibitors. Their mode of action is under investigation in order to examine their potential in drug design for diseases related to overwhelming XO action. Introduction Xanthine oxidase (XO) is a flavoprotein, which belongs to molybdenum hydroxylase superfamily and consists of two identical subunits of 145 kDa. Each subunit of the molecule is Varenicline Hydrochloride composed of an N-terminal 20-kDa domain containing two iron-sulfur clusters, a central 40-kDa FAD-binding domain and a C-terminal 85-kDa molybdopterin-binding domain with the four redox centers aligned in an almost linear fashion. Its active form is a homodimer of 290 kDa with each of the monomers acting independently in catalysis [1]. XO is a cytosolic enzyme present in various species, namely bacteria, higher plants, invertebrates and vertebrates [2]. It is also present in several mammalian tissues such as liver, intestine, kidney, lungs, myocardium, brain, plasma and erythrocytes. Among them, XO activity is highest in liver and intestine [3]. XO is the enzyme, which participates in purine degradation, is the main contributor of free radicals during exercise [4], [5]. It uses molecular oxygen as the electron acceptor thereby resulting in production of superoxide radical (O2 ??) and hydrogen peroxide (H2O2) [4]. However, XO also results in uric acid production which constitutes the most abundant antioxidant molecule in plasma. Thus, the role of XO in redox status is unequivocal since its activity leads to the production of both free radicals and uric acid. Furthermore, XO exhibits a broad specificity toward oxidation of a wide variety of heterocyclic compounds such as purines and pteridines [6], [7] and numerous aliphatic and aromatic aldehydes to the corresponding carboxylic acid [8], [9]. Therefore, it participates in the detoxification of endogenous compounds and xenobiotics. XO is considered as a major contributor of free radicals in various pathological conditions. More specifically, XO has been implicated in several diseases including ischemia-reperfusion injury, myocardial infarction, hypertension, atherosclerosis, diabetes and cancer [1]. As it has Emcn been previously stated XO results not only in free radical production but also in uric acid generation. Gout is a condition where excessive uric acid formation leads to its crystallization and deposition of uric acid crystals in the joints, the connective tissues and the kidneys [10]. Thus, the inhibition of XO activity may have simultaneously antiradical and inhibitory properties with therapeutic interest. The most commonly used and well studied XO inhibitor is allopurinol [11], [12]. Allopurinol [4-hydroxypyrazolo (3,4-d) pyrimidine] is a structural analogue of hypoxanthine [13]. It inhibits the conversion of hypoxanthine Varenicline Hydrochloride to xanthine to uric acid thus decreasing uric acid concentration. It is the only specific competitive, non natural XO inhibitor and is widely used as a drug. Moreover, due to its property to inhibit O2 ?? production, via XO inhibition, allopurinol is considered as a potent antioxidant [5]. However, this is controversial because allopurinol is also considered as a prooxidant molecule because it leads to inhibition of uric acid production as well [14]. Recently, a lot of research has been conducted in order to discover new, natural and specific XO inhibitors [1]. Numerous plant components [15], [16] and polyphenolic compounds, especially flavonoids [17], [18], have been previously examined for his or her inhibitory properties against XO activity. Legumes constitute an important source of polyphenols including flavonoids (kaempferol, quercetin, anthocyanins and tannins), flavonoid glycosides, isoflavones, phenolic acids and lignans [19], [20]. Inside a earlier Varenicline Hydrochloride study in our study group, several components derived from family vegetation cultivated in Greece have been analyzed for his or her antioxidant and chemopreventive properties [21]. More specifically, family plant components and 14 fractions rich in polyphenolic compounds isolated from 2 of them exhibited potent antiradical and chemopreventive properties and safeguarded DNA against free radical-induced damage [21], [22]. In extending these studies, we examined the effects of some of the aforementioned components on XO activity. From the results obtained, the components exhibited potent inhibitory activity on XO implying that polyphenols present in them are responsible for their.