Pyrimidine Glycosides Research Articles

الفافزم ونقص انزيم glucose-6-phosphate dehydrogenase

Favism disease, also known as hemolytic syndrome (the breakdown of red blood cells) affects some people (especially male children) when they consume the fava beans (fava bean, broad bean) because they contain high concentrations of pyrimidine glycosides (vicine and convicine) or they take some medications or an imbalance in metabolism or infections. causing the generation of harmful oxygen forms, as these people suffer from a deficiency in the glucose-6-phosphate dehydrogenase (G6PD) enzyme, which is responsible for the availability of, NADPH, which is important in providing reduced glutathione forms, (GSH), as the latter contributes to the conversion of H2O2 into O2 and H2O, and thus prevents the harmful effects of oxidation in red blood cells, represented by their destruction. Symptoms include nausea, pale jaundice, and dark urine. the severity of the disease varies between patients, and the severity of episodes can vary in the same patient, therefore, diagnosing G6PD deficiency and educating the patient regarding safe and unsafe medications and foods is critical to prevent recurring episodes.

Distribution of Vicine, Convicine and Levodopa in Faba Bean Plant Tissues Determined by UltraHigh Performance Liquid Chromatography-Electrospray Ionization Mass Spectrometry

Faba bean is an emerging pulse crop for the Canada Prairies and is becoming an increasingly important source of plant sourced protein. It also has a high content of levodopa (up to 0.1 % of the dry seed weight), a nutraceutical compound for treating Parkinson's Disease (PD). The presence of pyrimidine glycosides, vicine and convicine, however, restricts the use of faba due to their potential to cause favism in susceptible individuals. For the rapid separation and quantification of levodopa, vicine and convicine, a 5-min ultrahigh performance liquid chromatography-electrospray ionization mass spectrometry method (UHPLC-ESI MS) was developed. This method provided a wide linear range of quantification (4.8 nM to 60 µM for vicine, and 6.0 nM to 24 µM for convicine and levodopa), and low limit of detection (1.2 to 3.0 nM). The method was applied in the analysis of diverse faba bean samples, from dehulled mature faba bean and seed coat, to fresh plant tissues such as flowers, leaves, stems, roots and pods. The results indicated that fresh faba bean plant tissues, such as leaves and flowers, had the highest concentration of levodopa and low level of VC, which makes them an alternative source of plant-based l-DOPA with potential as a food-based treatment for Parkinson's Disease.

Effect of Lactic Acid Bacteria on the Level of Antinutrients in Pulses: A Case Study of a Fermented Faba Bean-Oat Product.

The importance of cereals and pulses in the diet is widely recognized, and consumers are seeking for ways to balance their diet with plant-based options. However, the presence of antinutritional factors reduces their nutritional value by decreasing the bioavailability of proteins and minerals. This study's aim was to select microbes and fermentation conditions to affect the nutritional value, taste, and safety of products. Single lactic acid bacteria (LAB) strains that reduce the levels of antinutrients in faba bean and pea were utilized in the selection of microbes for two starter mixtures. They were studied in fermentations of a faba bean-oat mixture at two temperatures for 24, 48, and 72 h. The levels of antinutrients, including galacto-oligosaccharides and pyrimidine glycosides (vicine and convicine), were determined. Furthermore, a sensory evaluation of the fermented product was conducted. Fermentations with selected single strains and microbial mixtures showed a significant reduction in the content of antinutrients, and vicine and convicine decreased by up to 99.7% and 96.1%, respectively. Similarly, the oligosaccharides were almost completely degraded. Selected LAB mixtures were also shown to affect the product's sensory characteristics. Microbial consortia were shown to perform effectively in the fermentation of protein-rich materials, resulting in products with improved nutritional value and organoleptic properties.

Degradation of pyrimidine glycosides and L-DOPA in the faba bean by Rhizopus oligosporus

Faba bean is an excellent source of nutrients, however, it contains some undesired compounds which still remain a concern. The aim of this study was to investigate the possibility of reducing the content of l-DOPA and pyrimidine glycosides by applying fermentation using three strains of Rhizopus oligosporus namely ATCC 48012, ATCC 42222 and ATCC 22959. The formation of potentially harmful degradation products during fermentation in the model conditions was also monitored. Results show that all investigated strains caused a significant decrease in the content of these compounds. A complete l-DOPA degradation was achieved within 2 days. In the case of vicine and convicine, a significant reduction was observed after 6 days, by 91 and 98%, respectively. Moreover, the LC-MS analysis allowed to detect carboxysalsolinol, divicine, and isouramil, as degradation products created during fermentation. This is the first report, where fermentation by Rhizopus oligosporus was applied in order to improve faba beans’ nutritional value, by decreasing l-DOPA and pyrimidine glycosides.

Synthesis of some novel phenylfuro[3,2-d]pyrimidine glycosides derivatives with expected antimicrobial activity

Reaction of ethyl 3-amino-5-phenylfuran-2-carboxylate 1 with benzoyl isothiocyanate gave 2,3-dihydro-6-phenyl-2-thioxofuro[3,2-d]pyrimidin-4-one. Compound 3 was reacted with benzyl chloride to afford 2-(benzylthio)-6-phenylfuro[3,2-d]pyrimidin-4-one 4 and also reacted with bromoglucopyranosyl to give S-glycoside 5. The cyclization of ethyl 3-amino-5-phenylfuran-2-carboxylate 1 using thiourea, aniline, and carbon disulfide gave phenylfuro[3,2-d]pyrimidine derivatives. The pharmacological properties for the synthesized compounds were reported.

Efficient extraction of vicine from faba beans using reactive system of high-pressure CO2/water

Vicine from faba bean is a causative agent of favism, a genetic disease, which manifests as hemolytic anemia. Despite that low vicine varieties of faba bean exist, they are not widely cultivated. Several extraction methods of vicine from faba beans have been presented in the literature, however, their low efficiency associated to time-consuming and costly process limit the practical use. This work for the first time addresses the employment of high-pressure CO2-assisted extraction of the pyrimidine glycosides from the faba bean. For this purpose, the effect of temperature, CO2 pressure and time on vicine extraction was scrutinized using Box-Behnken design of experiments. Response surface methodology was used to determine the optimal extraction conditions. At 40.7 °C, 8.1 bar of CO2 pressure and 5.1 min of extraction, 81% of total vicine should be extracted from faba bean.

Synthesis and Anti-HBV Activity of Novel Substituted Pyrimidine Glycosides and Their Acyclic Analogues

New aryl substituted uracil and thiouracil glycosides are synthesized by glycosylation at N1 in the pyrimidine nucleus using glycopyranosyl halides in basic medium. In addition C-linked hydrazinyl acyclic sugar derivatives exhibiting different sugar moieties, attached at C6, are also prepared. Antiviral activity of the newly synthesized compounds is studied against Hepatitis B virus (HBV). The antiviral tests data indicated high activity of compounds 6b, 6c and 12a–12c with mild cytotoxic effects. The influence of glycosyl moieties attached to the substituted pyrimidine system in addition to the substitution at the aryl fragment on activity is discussed.

Rapid analysis of medically relevant compounds in faba bean seeds using FAIMS and mass spectrometry

Faba bean (Vicia faba L.) has potential to expand globally because of its ability to provide nutritional benefits through its high amounts of seed protein, carbohydrates and dietary fiber. The seeds also contain levodopa, a treatment for Parkinson’s disease. Faba bean consumption is limited primarily because the seeds contain the pyrimidine glycosides, vicine and convicine (v-c), which can cause favism in people with a genetically inherited glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD deficiency is inherited as an X–linked recessive allele and susceptible individuals develop anaemia when they consume faba beans. Faba bean cultivars with reduced levels of v-c are available, but it is difficult to maintain genetic isolation because the plants can be cross-pollinated by bees. The seed supplies of low v-c seed stocks and foods derived from them must be monitored to ensure maintenance of low v-c. Here we report a rapid, robust method to measure vicine, convicine, and levodopa using high-field asymmetric waveform ion mobility spectrometry (FAIMS) coupled with flow injection analysis and mass spectrometry that has an analysis step of 54 s. With the addition of a methanol gas modifier in FAIMS, vicine and convicine were separated in the gas-phase and then measured by tandem mass spectrometry. More than 40 genotypes representing diverse faba bean germplasm were quantified. Convicine showed the widest concentration range (~520X) and all analytes showed good reproducibility illustrating that this method can be routinely used to simultaneously screen for v-c and quantify L-DOPA, thereby ensuring food safety.

Quantification of vicine and convicine in faba bean seeds using hydrophilic interaction liquid chromatography

Faba bean (Vicia faba L.) provides environmental and health benefits; however, the presence of the pyrimidine glycosides vicine and convicine (v-c) in its seeds limits consumption. Low v-c genotypes have been introduced, but the convicine levels in these genotypes have not been quantified. To improve detection, the polar nature of v-c was exploited by implementing hydrophilic interaction liquid chromatography (HILIC). A sample preparation method using a two-step extraction was developed for use with UV and/or tandem mass spectrometry (SRM) detection. The HILIC-UV method was suitable for over three orders of magnitude, covering the range of v-c concentrations in faba bean seeds across all genotypes tested. The linear range of HILIC-SRM was slightly less (∼3 orders of magnitude), but improved sensitivity and selectivity make it more suitable for quantifying low v-c samples. The analysis of 13 genotypes suggests that v-c concentrations in faba bean seeds may be independent quantitative traits.

Degradation of vicine, convicine and their aglycones during fermentation of faba bean flour.

In spite of its positive repercussions on nutrition and environment, faba bean still remains an underutilized crop due to the presence of some undesired compounds. The pyrimidine glycosides vicine and convicine are precursors of the aglycones divicine and isouramil, the main factors of favism, a genetic condition which may lead to severe hemolysis after faba bean ingestion. The reduction of vicine and convicine has been targeted in several studies but little is known about their degradation. In this study, the hydrolysis kinetics of vicine and convicine and their derivatives during fermentation with L. plantarum DPPMAB24W was investigated. In particular, a specific HPLC method coupled to ESI-MS and MS/MS analysis, including the evaluation procedure of the results, was set up as the analytical approach to monitor the compounds. The degradation of the pyrimidine glycosides in the fermented flour was complete after 48 h of incubation and the aglycone derivatives could not be detected in any of the samples. The toxicity of the fermented faba bean was established through ex-vivo assays on human blood, confirming the experimental findings. Results indicate that mild and cost effective bioprocessing techniques can be applied to detoxify faba bean also for industrial applications.

Flanking SNP markers for vicine–convicine concentration in faba bean (Vicia faba L.)

The pyrimidine glycosides, vicine and convicine, limit the use of faba bean (Vicia faba L.) as food and feed. A single recessive gene, vc-, is responsible for a lowered vicine–convicine concentration. The biosynthetic pathway of these closely related compounds is not known, and the nearest available markers are several cM away from vc-. Improved markers would assist breeding and help to identify candidate genes. A segregating population of 210 F5 recombinant inbred lines was developed from the cross of Mélodie/2 (low vicine–convicine) × ILB 938/2 (normal vicine–convicine), and vicine–convicine concentrations were determined twice on each line. The population was genotyped with a set of 188 SNPs. A strong, single QTL for vicine–convicine concentration was identified on chromosome I, flanked by markers 1.0 cM away on one side and 2.6 cM on the other. The interval defined by these markers in the model species Medicago truncatula includes about 340 genes, but no candidate genes were identified. Further fine mapping should lead to the identification of tightly linked markers as well as narrowing down the search for candidate regulatory or biosynthetic genes which could underlie the vc- locus.

Effect of Roasting and Boiling on the Content of Vicine, Convicine and L‐3,4‐dihydroxyphenylalanine in Vicia fabaL.

AbstractThe pyrimidine glycosides, vicine and convicine, are compounds of the genus Vicia, whereas their aglycone derivatives, divicine and isouramil, are responsible for favism occurrence, and L‐3,4‐dihydroxyphenylalanine (L‐DOPA) is a nonprotein amino acid precursor of dopamine in healthy neurons. The present work evaluated the effect of thermal treatment, which consisted of roasting and boiling, on the content of vicine, convicine and L‐DOPA in mature cotyledons of 10 varieties of Mexican Vicia faba L. and determined the concentration of glycosides and L‐DOPA by high‐performance liquid chromatography. The raw cotyledons showed 2.88–6.10, 0.63–1.68 and 0.28–0.44 vicine, convicine and L‐DOPA, respectively. The 12 and 40% and 30 and 61% decrease in vicine and convicine content, respectively, were observed to be the effect of roasting and boiling the samples. L‐DOPA was totally removed by both thermal processes. In all analyzed samples, vicine was the main compound; however, there were significant differences between varieties and thermal treatments.Practical ApplicationsVicine and convicine glycosides are strongly implicated in favism, a hemolytic anemia in humans, and in poor performance of laying hens. There are reports of decreased egg weight, increase in the fragility of the yolk and a number of blood stains, and decreased fertility and hatchability of eggs. The characterization of new varieties of faba bean in their content of potentially toxic glycosides allows selection of those with the lowest possible content of such compounds. Also, the application of heat treatments that reduce glycosides will allow the use of seeds or flour to develop harmless food and feed ingredients.

Synthesis and antiviral activity of new substituted pyrimidine glycosides

AbstractA number of N‐substituted pyrimidine glycosides were synthesized by coupling reaction of the pyrimidine base with acetobromosugars followed by deprotection. The synthesized compounds were tested for their antiviral activity against Hepatitis B Virus (HBV). Plaque reduction infectivity assay was used to determine virus count reduction as a result of treatment with tested compounds which showed moderate to high anti viral activities. J. Heterocyclic Chem., (2011).

A genomic approach to nutritional, pharmacological and genetic issues of faba bean (Vicia faba): Prospects for genetic modifications

Cultivated faba bean (Vicia faba) is widely used as human food, especially in Europe, Northern Africa and China. In view of its superior feeding value over field peas or other legumes, it is also widely used as animal feed for a variety of species. V. faba also contains medically important components such as 3,4-dihydroxyphenylalanine (levo-DOPA, L-DOPA), the principal treatment used for Parkinson’s disease patients. However, this species also contains several antinutritional components, including the pyrimidine glycosides vicine and convicine; phytates; and the sucrose galactosides including raffinose, stachyose and verbascose. We have undertaken a genomic project to provide publicly available expressed sequence tag sequences (EST) prepared from early to mid developing embryo in an attempt to identify genes that are likely to be involved in the biosynthesis of L-DOPA and the vicine group of compounds. As initial examples of the utility of this approach, we describe the complete sequence of fabatin, new defensins, type 4 metallothioneins and a variety of other key genes which were identified in this EST library. No candidate sequences corresponding to the biosynthesis of L-DOPA or the vicine group could be identified at this early stage of seed development.

ChemInform Abstract: Synthesis and Evaluation of Antimicrobial Activity of Some Pyrimidine Glycosides.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis and Evaluation of Antimicrobial Activity of Some Pyrimidine Glycosides

Reaction of ethyl 4-thioxo-3,4-dihydropyrimidine-5-carboxylate derivatives 1a,b and ethyl 4-oxo-3,4-dihydropyrimidine-5-carboxylate 1c with 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide in KOH or TEA afforded ethyl 2-aryl-4-(2′,3′,4′,6′-tetra-O-acetyl-β-D-glucopyranosylthio or/ oxy)-6-methylpyrimidine-5-carboxylate 6a-c. The glucosides 6a and 6b were obtained by the reaction of 1a and 1b with peracetylated glucose3 under MW irradiation. Mercuration of 1a followed by reaction with acetobromoglucose gave the same product 6a. The reaction of 1a-c with peracetylated ribose 4 under MW irradiation gave ethyl 2-aryl-4-(2′,3′,5′-tri-O-acetyl-β-D-ribofuranosylthio)-6-methylpyrimidine-5-carboxylate 8a–c. The deprotection of 6a–c and 8a–c in the presence of methanol and TEA/H2O afforded the deprotected products 7a–c and 9a–c. The structure were confirmed by using 1H and 13CNMR spectra. Selected members of these compounds were screened for antimicrobial activity.

A novel one-step synthesis of thioquinazoline glycosides and pyrazolopyrimidine glycoside analogs.

The reaction of glycosyl isothiocyanates (1a, b, c) with anthranilic acid gave corresponding glycosyl thioquinazolines (3a, b, c) in the presence of zinc chloride in excellent yields. The reaction performed in the absence of zinc chloride afforded the intermediate glycosyl thioureides (2a, b) along with the cyclized compounds. However, similar treatment of 1a with 2-amino-3-carboethoxypyridine did not give the corresponding glycosyl pyridopyrimidine (5a), but glycosyl thioureide (4a) was obtained in good yield. Attempted ring closure of 4a under neutral or acidic conditions failed. Similar reactions of 1a, b, and c with 3-aminopyrazole-4-carboxylic acid in the presence of zinc chloride afforded corresponding pyrazolo [4, 3-e] pyrimidine glycosides (6a, b and c) in fair yields.

Molecular orbital calculations on the conformation of nucleic acids and their constituents: I. Conformational energies of β-nucleosides with C(3′)- and C(2′)-endo sugars

Molecular orbital calculations, using the all-valence-electrons PCILO method, are carried out for the evaluation of conformational energies of purine and pyrimidine nucleosides as a function of the rotation about the C-N glycosidic linkage. In distinction to previous empirical treatments which were based on the partitioning of the potential energy into different constituents and a separate evaluation of those, the quantum-mechanical computations provide directly the total molecular energy corresponding to the different geometrical arrangements of the atoms. Explicit distinction is also made in the calculations for cases in which an intramolecular hydrogen bond is or is not formed between the sugar and base. Evaluation of the conformation energies is completed by evaluation of the relative probabilities of finding the nucleosides in the anti or syn regions. Results are presented for purine and pyrimidine glycosides with C(3′)-endo and C(2′)-endo sugars and compared with the available experimental data from X-ray studies on crystals.

185. Experiments on the synthesis of purine nucleosides. Part XV. The configuration of some synthetic purine and pyrimidine glycosides

185. Experiments on the synthesis of purine nucleosides. Part XV. The configuration of some synthetic purine and pyrimidine glycosides