Purine Compounds Research Articles

Glioblastoma multiforme: Metabolic differences to peritumoral tissue and IDH-mutated gliomas revealed by mass spectrometry imaging.

Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor. High infiltration rates and poor therapy responses make it the deadliest glioma. The tumor metabolism is known to differ from normal one and is influenced through various factors which can lead to longer survival. Metabolites are small molecules (< 1500 Da) that display the metabolic pathways in the tissue. To determine the metabolic alterations between tumor and peritumoral tissue in human GBMs, mass spectrometry imaging (MSI) was performed on thin sections from 25 resected tumors. In addition, the GBMs were compared with six gliomas harboring a mutation in the isocitrate dehydrogenase (IDH1) gene (IDH1). With this technique, a manifold of analytes can be easily visualized on a single tissue section. Metabolites were annotated based on their accurate mass using high resolution MSI. Differences in their mean intensities in the tumor and peritumoral areas were statistically evaluated and abundances were visualized on the tissue. Enhanced levels of the antioxidants ascorbic acid, taurine, and glutathione in tumor areas suggest protective effects on the tumor. Increased levels of purine and pyrimidine metabolism compounds in GBM areas indicate the high energy demand. In accordance with these results, enhanced abundances of lactate and glutamine were detected. Moreover, decreased abundance of N-acetylaspartate, a marker for neuronal health, was measured in tumor areas. Obtained metabolic information could potentially support and personalize therapeutic approaches, hence emphasizing the suitability of MSI for GBM research.

Phytochemical screening of extracts from Spiranthera odoratissima A. St.-Hil. (Rutaceae) leaves and their in vitro antioxidant and anti-Listeria monocytogenes activities

Spiranthera odoratissima A. St.-Hil (Rutaceae), a shrub whose common name is manacá do Cerrado in Brazilian Portuguese, is about 1-m high and has been used by folk medicine to treat stomachache, kidney and liver infections, headache, rheumatism and as a blood purifier. This study aimed at preparing hexane, ethyl acetate, methanolic, hydroethanolic and aqueous extracts from S. odoratissima leaves, at carrying out preliminary phytochemical screening and at evaluating their in vitro antioxidant and anti-Listeria monocytogenes activities. Antioxidant activity was evaluated by the DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS (2,2-azinobis-3-ethybenzothiazoline-6-sulfonate) and FRAP (ferric reducing antioxidant power) methods. Antibacterial activity was investigated against L. monocytogenes and Minimum Inhibitory Concentration (MIC) values of plant extracts were calculated by the broth microdilution method with the use of 96-well plates. In aqueous, methanolic, hydroethanolic, ethyl acetate and hexane extracts from S. odoratissima leaves, the following classes of compounds were investigated: organic acids, reducing sugars, flavonoids, saponin compounds, coumarin compounds, phenolics, tannins, purine compounds, catechins, flavonol derivatives, sesquiterpene lactones and anthraquinones. All plant extracts, except the hexane one, exhibited high antioxidant activity. Regarding antibacterial activity, the most polar extracts showed high activity against L. monocytogenes; their MIC values ranged between 12.5 and 62.5 µg mL-1, while the hexane one exhibited low activity (MIC = 1000 µg mL-1). In short, extracts from S. odoratissima leaves may be considered promising sources of secondary metabolites with relevant antioxidant and antibacterial activities.

Purinergic signalling selectively modulates maintenance but not repair neurogenesis in the zebrafish olfactory epithelium.

Olfactory sensory neurons (OSNs) of the vertebrate olfactory epithelium (OE) undergo continuous turnover but also regenerate efficiently when the OE is acutely damaged by traumatic injury. Two distinct pools of neuronal stem/progenitor cells, the globose (GBCs), and horizontal basal cells (HBCs) have been shown to selectively contribute to intrinsic OSN turnover and damage-induced OE regeneration, respectively. For both types of progenitors, their rate of cell divisions and OSN production must match the actual loss of cells to maintain or to re-establish sensory function. However, signals that communicate between neurons or glia cells of the OE and resident neurogenic progenitors remain largely elusive. Here, we investigate the effect of purinergic signaling on cell proliferation and OSN neurogenesis in the zebrafish OE. Purine stimulation elicits transient Ca2+ signals in OSNs and distinct non-neuronal cell populations, which are located exclusively in the basal OE and stain positive for the neuronal stem cell marker Sox2. The more apical population of Sox2-positive cells comprises evenly distributed glia-like sustentacular cells (SCs) and spatially restricted GBC-like cells, whereas the more basal population expresses the HBC markers keratin 5 and tumor protein 63 and lines the entire sensory OE. Importantly, exogenous purine stimulation promotes P2 receptor-dependent mitotic activity and OSN generation from sites where GBCs are located but not from HBCs. We hypothesize that purine compounds released from dying OSNs modulate GBC progenitor cell cycling in a dose-dependent manner that is proportional to the number of dying OSNs and, thereby, ensures a constant pool of sensory neurons over time.

Reduksi Purin pada Emping Melinjo Melalui Pre-treatment Perendaman Emping Mentah

Melinjo chips (emping as local name) has high purine content which can be related to the high uric acid level in blood that lead to joint inflamation due to the sendimentation of uric acid. The objective of this research is to prove that soaking process can reduce purine content in emping and to know the effect of the soaking process length in purine reduction. Soaking time (2, 5, and 12 hours) and emping brand (Sriti, A1 and Koki) were used as the treatments. Purine compounds such as adenine and hypoxanthine were analyzed by using High Performance Liquid Chromatography (HPLC) method with C18 column and UV detector. The three emping samples were also analyzed by using sensory evaluation to know the consumer preference toward the treated fried emping. Results obtained from this research were that soaking process can reduce both adenine and hypoxanthin content in emping. Soaking for 2 hours in water could reduce adenine content 13 – 39% and hypoxanthine content 4 – 60%. Soaking process for 2 hours on emping could reduce up to 50% of total purine base content in A1 brand, however, soaking time was not directly proportional to the decrease in purine levels. Purine content after 5 and 12 hours soaking tend to be fluctuative. Emping samples that were soaked in the water have a decrease in preference by the panelists either in color, aroma, taste, texture or in overall, but still accepted by panelists.

Degradation and DBP formations from pyrimidines and purines bases during sequential or simultaneous use of UV and chlorine

Purine and pyrimidines are present an important pool of dissolved organic nitrogen in aqueous medias and also precursors of disinfection byproducts. The degradation kinetics of cytosine and adenine—model pyrimidine and purine compounds—were investigated along with their transformation pathways leading to the formation of disinfection byproducts during two typical multi-barrier disinfection processes: UV irradiation and UV/chlorine pretreatment followed by post-chlorination. UV irradiation followed by post-chlorination enhanced the degradation of cytosine and adenine (by 17.1 and 26.1%, respectively), but it also generated more byproduct precursors compared to chlorination alone. The presence of reactive species in the UV/chlorine treatment greatly enhanced cytosine and adenine degradation (by 61.8 and 123.0%) but generated even more disinfection byproducts. Compared to 24 h chlorination, the concentrations of byproducts increased by up to 361.6% for cytosine and 85.1% for adenine with longer UV/chlorine treatment (from 2 to 30 min). Thirty minutes of combined UV/chlorine treatment decreased the total organic chlorine produced from cytosine by 34.4% (from 233.8 to 153.3 μg Cl L−1) but it increased byproduct generation by 68.3% compared with 24 h of simple chlorination. The TOCl from adenine increased by 50.0% (from 9.2 to 18.4 μg Cl L−1) but byproduct generation was 11.0% less after 30 min of UV/chlorine pretreatment followed by 24 h of chlorination. The intermediates generated were analyzed in detail and multiple transformation pathways leading to byproduct formation are proposed.

Layer-by-Layer Assembly of SAM-supported Porphyrin-based Metal Organic Frameworks for Molecular Recognition

The development of the sensing systems based on the ultrathin films of functional metal organic networks as efficient synthetic alternative to molecular biosensors is in the focus of intense research. Herein we report how to fabricate uniformly structured surface-attached metal organic frameworks (SURMOFs) from zinc complex of meso-carboxyphenyl-substituted porphyrin and zinc acetate as films on the surface of self-assembled monolayers of silanes and thiols. The layer-by-layer self-assembly with shortened time of the layer deposition at room temperature was applied to obtain 5-layer SURMOFs with high crystallinity, which was confirmed by X-ray diffraction. These SAM-supported SURMOF films were used as sensing layers for qualitative response to organic molecules in aqueous solutions. By using surface plasmon resonance spectroscopy, we showed that the SURMOFs do not bind 4-nitrophenol and uracil whereas they are capable of absorption of purine compounds such as adenine and adenosine 5-monophosphate. This binding is a size sensitive process in favor to adenine suggesting the effect of the SURMOF structure on the molecular recognition. The UV-vis spectroscopy study of the process indicated that the recognition of purines by the porphyrin-based SURMOF proceeds through the interactions of the amine groups with zinc ions in metal clusters rather than with the central metal ions in porphyrin cores. Our findings provide an insight into the sensing properties of the porphyrin-based SURMOFs that is useful for further advancements in fabrication of responsive thin films for biologically relevant analytes.

Extracellular ATP and β-NAD alter electrical properties and cholinergic effects in the rat heart in age-specific manner.

Extracellular ATP and nicotinamide adenine dinucleotide (β-NAD) demonstrate properties of neurotransmitters and neuromodulators in peripheral and central nervous system. It has been shown previously that ATP and β-NAD affect cardiac functioning in adult mammals. Nevertheless, the modulation of cardiac activity by purine compounds in the early postnatal development is still not elucidated. Also, the potential influence of ATP and β-NAD on cholinergic neurotransmission in the heart has not been investigated previously. Age-dependence of electrophysiological effects produced by extracellular ATP and β-NAD was studied in the rat myocardium using sharp microelectrode technique. ATP and β-NAD could affect ventricular and supraventricular myocardium independent from autonomic influences. Both purines induced reduction of action potentials (APs) duration in tissue preparations of atrial, ventricular myocardium, and myocardial sleeves of pulmonary veins from early postnatal rats similarly to myocardium of adult animals. Both purine compounds demonstrated weak age-dependence of the effect. We have estimated the ability of ATP and β-NAD to alter cholinergic effects in the heart. Both purines suppressed inhibitory effects produced by stimulation of intracardiac parasympathetic nerve in right atria from adult animals, but not in preparations from neonates. Also, ATP and β-NAD suppressed rest and evoked release of acetylcholine (ACh) in adult animals. β-NAD suppressed effects of parasympathetic stimulation and ACh release stronger than ATP. In conclusion, ATP and β-NAD control the heart at the postsynaptic and presynaptic levels via affecting the cardiac myocytes APs and ACh release. Postsynaptic and presynaptic effects of purines may be antagonistic and the latter demonstrates age-dependence.

Dissolution of Bioactive Components from Dried Fruiting Bodies of the Culinary-Medicinal Shiitake Mushroom, Lentinus edodes (Agaricomycetes), during Cleaning, Soaking, and Cooking.

Lentinus edodes fruiting bodies are rich in active substances such as polysaccharides and eritadenine. Patients with gout, however, should avoid or severely limit their intake of foods containing large amounts of purine. In this study we quantitatively analyzed the polysaccharide and purine compounds dissolved from L. edodes fruiting bodies during cleaning, soaking, and cooking. Eritadenine, adenosine, guanosine, guanosine monophosphate, adenosine monophosphate, xanthine, and adenine dissolved from L. edodes fruiting bodies during cleaning with tap water; their dissolution rates ranged between 3.77% and 24.30%. Dissolution rates of polysaccharide and purine compounds in L. edodes fruiting bodies increased linearly with increases in the duration of soaking and cooking, and adding acetic acid or NaHCO3 in the soaking or cooking solutions significantly either inhibited or promoted their dissolution rates. On the basis of these experimental results, we offer science-based suggestions for reasonable treatment of L. edodes fruiting bodies before eating for both patients with gout and healthy people.

Pain, Hyperuricemia (Uric Acid), and Elderly Insomnia

Hyperuricemia is a result of normal metabolism from the digestion of proteins from the decomposition of purine compounds which should be removed through the kidneys, feces, sweat and urine. The accumulation of too much purine substances causes pain that occurs a lot in the age above 45 years, namely the elderly. Elderly who experience Hyperuricemia is one sign of symptoms is pain. Pain can cause elderly people who have difficulty sleeping or insomnia. Purpose of the study Analyze the relationship of pain with insomnia in elderly patients with Hyperuricemia. The design of the analytical study of correlation with the Cross Sectional approach. The population is all Hyperuricemia sufferers in the elderly in Ledok Area, Sukorejo Village, Malo District, Bojononegoro Regency using total sampling technique. Data were collected using questionnaire sheets with measuring instruments Numeral Rating Scale (NRS) and Pittsburgh Sleep Quality Index (PSQI) Questionnaire, to determine the relationship of pain with insomnia in elderly patients with Hyperuricemia. The analysis uses the Pierson test with a significance level of α <0.05. Nearly half of respondents aged 55–64 years experienced insomnia with poor sleep quality as many as 13 respondents (43.3%) experienced by female respondents as many as 12 respondents (40%) and 1 male respondent (0.3%) and some women who have a value of Hyperuricemia levels of 6–7 mg/dL with a moderate pain scale of 14 respondents (46.7%). The results of this study were that there was a relationship between pain and insomnia in elderly patients with Hyperuricemia with the results of the Pearson test obtained sig. 2 p = 0, 000 <α <0, 05.

Extracellular Diadenosine Tetraphosphate Suppresses Ectopic Proarrhythmicity in the Myocardial Tissue of the Pulmonary Veins in Adult but not in Neonatal Rats

Diadenosine tetraphosphate (Ap4A) belongs to a group of endogenous purine compounds that have recently been considered as new neurotransmitters or cotransmitters in the autonomic nervous system. It has been shown that Ap4A affects electrophysiology of a pacemaker and working myocardium and modulates adrenergic control of the heart in adult mammals. Nevertheless, the physiological role of Ap4A in the regulation of bioelectric properties in the pulmonary vein (PV) myocardium has not yet been investigated. It is well known that myocardial tissue in the wall of the PV acts as source of the ectopic proarrhythmic activity that underlies supraventricular arrhythmias like atrial fibrillation. The aim of the present study was to elucidate the effects Ap4A on bioelectrical properties and proarrhythmic ectopy in PVs in adult rats and at early postnatal ontogenesis. Thus, the resting potentials and the electrically evoked and spontaneous action potentials were recorded with the use of the standard microelectrode technique in multicellular isolated PV specimens from male Wistar rats at postnatal days 1-, 7-, 14-, and 21- and also from 60-day-old animals, which were considered as mature. The application of Ap4A caused significant reduction of action potential duration in PV specimens from rats of all ages. Ap4A also caused significant resting membrane potential hyperpolar-ization in quiescent PVs specimens from 14-, 21-, and 60-day-old rats. In addition, Ap4A caused complete and significant suppression of ectopic automaticity caused by preliminary noradrenaline administration in PV from 21- and 60-day-old rats, but Ap4A was unable to alter spontaneous intrinsic activity in PV from neo-nate (1-day-old) rats. The Ap4A-caused attenuation of noradrenaline-induced ectopy in PV was accompanied by substantial resting membrane potential hyperpolarization in all cases. Our results allow suggesting that the release of Ap4A as a cotransmitter from autonomic nerve endings can reduce proarrhythmic ectopy caused by sympathetic stimulation of the PV myocardium in vivo.

Machine-Learning Identification of the Sensing Descriptors Relevant in Molecular Interactions with Metal Nanoparticle-Decorated Nanotube Field-Effect Transistors.

Carbon nanotube-based field-effect transistors (NTFETs) are ideal sensor devices as they provide rich information regarding carbon nanotube interactions with target analytes and have potential for miniaturization in diverse applications in medical, safety, environmental, and energy sectors. Herein, we investigate chemical detection with cross-sensitive NTFETs sensor arrays comprised of metal nanoparticle-decorated single-walled carbon nanotubes (SWCNTs). By combining analysis of NTFET device characteristics with supervised machine-learning algorithms, we have successfully discriminated among five selected purine compounds, adenine, guanine, xanthine, uric acid, and caffeine. Interactions of purine compounds with metal nanoparticle-decorated SWCNTs were corroborated by density functional theory calculations. Furthermore, by testing a variety of prepared as well as commercial solutions with and without caffeine, our approach accurately discerns the presence of caffeine in 95% of the samples with 48 features using a linear discriminant analysis and in 93.4% of the samples with only 11 features when using a support vector machine analysis. We also performed recursive feature elimination and identified three NTFET parameters, transconductance, threshold voltage, and minimum conductance, as the most crucial features to analyte prediction accuracy.

Emerging Role of Purine Metabolizing Enzymes in Brain Function and Tumors.

The growing evidence of the involvement of purine compounds in signaling, of nucleotide imbalance in tumorigenesis, the discovery of purinosome and its regulation, cast new light on purine metabolism, indicating that well known biochemical pathways may still surprise. Adenosine deaminase is important not only to preserve functionality of immune system but also to ensure a correct development and function of central nervous system, probably because its activity regulates the extracellular concentration of adenosine and therefore its function in brain. A lot of work has been done on extracellular 5′-nucleotidase and its involvement in the purinergic signaling, but also intracellular nucleotidases, which regulate the purine nucleotide homeostasis, play unexpected roles, not only in tumorigenesis but also in brain function. Hypoxanthine guanine phosphoribosyl transferase (HPRT) appears to have a role in the purinosome formation and, therefore, in the regulation of purine synthesis rate during cell cycle with implications in brain development and tumors. The final product of purine catabolism, uric acid, also plays a recently highlighted novel role. In this review, we discuss the molecular mechanisms underlying the pathological manifestations of purine dysmetabolisms, focusing on the newly described/hypothesized roles of cytosolic 5′-nucleotidase II, adenosine kinase, adenosine deaminase, HPRT, and xanthine oxidase.

Purine-Furan and Purine-Thiophene Conjugates

Furyl and thienyl moieties were introduced into a purine structure to elevate its fluorescence properties, while a trityl group was used to increase the amorphous properties of the purine compounds. The title compounds were prepared by a sequence involving a Mitsunobu, a SNAr and a Suzuki–Miyaura reaction and their photophysical properties were studied. Quantum yields in the solution reached up to 88% but only up to 5% in the thin layer.

Extracellular NAD+ Suppresses Adrenergic Effects in the Atrial Myocardium of Rats during the Early Postnatal Ontogeny.

The effects of sympathetic cotransmitter NAD+ (10 μM) on bioelectric activity of the heart under conditions of adrenergic stimulation were studied on isolated spontaneously contracting preparations (without stimulation) of the right atrium from 2-7-day-old rats. Action potentials were recorded in the working myocardium using standard microelectrode technique. Perfusion of the right atrium with norepinephrine solution (1 μM) altered the configuration and significantly lengthened the action potentials. NAD + against the background of norepinephrine stimulation significantly decreased the duration of action potentials, in particular, at 25% repolarization. The effect of purine compounds NAD + , ATP, and adenosine on bioelectrical activity of the heart of newborn rats was studied under basal conditions (without norepinephrine stimulation). The effect of NAD + against the background of adrenergic stimulation was more pronounced than under basal conditions and was probably determined by suppression of ICaL, which can be the main mechanism of NAD + action on rat heart.

Influence of gemcitabine chemotherapy on the microbiota of pancreatic cancer xenografted mice.

Pancreatic ductal adenocarcinoma (PDAC) represents the fourth cause of cancer-related death. We aimed to evaluate whether gemcitabine treatment shapes the gut microbiota in a model of PDAC xenografted mice. Pancreatic cancer xenograft mice were subjected to gemcitabine injection once per week for 3 weeks to assess the tumor volume as compared to control mice injected with normal saline solution. The composition of fecal microbiota, the activation of NF-kB pathway in cancer tissues and the serum metabolomics were further analyzed. Gemcitabine considerably decreases the proportion of Gram- positive Firmicutes (from about 39 to 17%) and the Gram- negative Bacteroidetes (from 38 to 17%) which are the two dominant phyla in the gut of tumor-bearing control mice. This downshift was replaced by an increase of Proteobacteria (Escherichia coli and Aeromonas hydrophila) from 15 up to 32% and Verrucomicrobia (Akkermansia muciniphila) from 5 to 33% in the gut of drug-receiving mice. An overall increase in inflammation-associated bacteria was observed upon gemcitabine. Consistently, activation of the NF-kB canonical pathway was found in cancer tissues from gemcitabine-treated mice. Serum metabolomics revealed a significant decrease of the purine compounds inosine and xanthine, and a decreasing trend for their metabolically-related molecule hypoxanthine. Understanding chemotherapy side effects may explain the lack of activity or the chemoresistant processes and it may help to set up strategies to improve the effectiveness of therapy.

Effects of Extracellular Diadenosine Tetraphosphate on Action Potentials in the Atrial and Ventricular Myocardium of the Rat Heart during Early Postnatal Ontogenesis

Diadenosine tetraphosphate (AP4A) belongs to a wide group of naturally derived endogenous purine compounds that have recently been considered as new neurotransmitters in the autonomic nervous system. It has been shown that AP4A induces inhibitory effects and modulates adrenergic control in the heart of adult mammals. Nevertheless, the physiological significance of AP4A in early postnatal development, when sympathetic innervation remains yet immature, has not been investigated. The aim of the present study was to elucidate the effects of AP4A on the heart bioelectrical activity in early postnatal ontogenesis. Action potentials (AP) were recorded using the standard microelectrode technique in multicellular isolated right atrial (RA), left atrial (LA), and ventricle (RV) preparations from male Wistar rats at postnatal days 1, 14, and 21 and from 60-day animals that were considered as adults. The application of AP4A caused significant reduction of AP duration in atrial (RA and LA) preparations from rats of all ages. Also, AP4A caused significant AP shortening in RV preparations from rats of various ages; however, the effect was more pronounced in 21-day-old and adult rats. AP4A failed to alter automaticity of RA preparations from the rats at postnatal days 1, 14, and 21 and weakly decreased spontaneous rhythm in RA preparations from the adult rats. The effect of AP4A was partially abolished by P2-receptor blocker PPADS in LA preparations from both 21-dayold and adult rats, while it failed to suppress AP4A-caused AP shortening in preparations from 1- and 14-dayold animals. Thus, extracellular AP4A causes shortening of AP both in the atrial and ventricular myocardium in the rats of early postnatal ontogenesis and in adults. The effect of AP4A depends on age only for ventricular myocardium where it may be attributed with growing contribution of diadenosine polyphosphates to the control of myocardium inotropy.

Purine analogs targeting the guanine riboswitch as potential antibiotics against Clostridioides difficile

Riboswitches recently emerged as possible targets for the development of alternative antimicrobial approaches. Guanine-sensing riboswitches in the bacterial pathogen Clostridioides difficile (formerly known as Clostridium difficile) constitute potential targets based on their involvement in the regulation of basal metabolic control of purine compounds. In this study, we deciphered the structure-activity relationship of several guanine derivatives on the guanine riboswitch and determined their antimicrobial activity. We describe the synthesis of purine analogs modified in ring B as well as positions 2 and 6. Their biological activity was determined by measuring their affinity for the C. difficile guanine riboswitch and their inhibitory effect on bacterial growth, including a counter-screen to discriminate against riboswitch-independent antibacterial effects. Altogether, our results suggest that improvements in riboswitch binding affinity in vitro do not necessarily translate into improved antibacterial activity in bacteria, despite the fact that some structure-activity relationship was observed at least with respect to binding affinity.

A sensitive turn on fluorescent probe for detection of biothiols using MnO2@carbon dots nanocomposites

Presently, the combination of carbon quantum dots (CQDs) and metal oxide nanostructures in one frame are being considered for the sensing of purine compounds. In this work, a combined system of CQDs and MnO2 nanostructures was used for the detection of anticancer drugs, 6-Thioguanine (6-TG) and 6-Mercaptopurine (6-MP). The CQDs were synthesized through microwave synthesizer and the MnO2 nanostructures (nanoflowers and nanosheets) were synthesized using facile hydrothermal technique. The CQDs exhibited excellent fluorescence emission at 420nm when excited at 320nm wavelength. By combining CQDs and MnO2 nanostructures, quenching of fluorescence was observed which was attributed to fluorescence resonance energy transfer (FRET) mechanism, where CQDs act as electron donor and MnO2 act as acceptor. This fluorescence quenching behaviour disappeared on the addition of 6-TG and 6-MP due to the formation of Mn-S bond. The detection limit for 6-TG (0.015μM) and 6-MP (0.014μM) was achieved with the linear range of concentration (0–50μM) using both MnO2 nanoflowers and nanosheets. Moreover, the as-prepared fluorescence-sensing technique was successfully employed for the detection of bio-thiol group in enapril drug. Thus a facile, cost-effective and benign chemistry approach for biomolecule detection was designed.

COMPUTATIONAL STUDIES OF PURINE DERIVATIVE USING MULTIFORMS OF HUMAN POLYPEPTIDES 1 AS TARGET ENZYME FOR ANTICANCER AGENTS

Objective: This research was conducted to prove and estimate the activity of the newly designed compound by applying quantitative structure–activity relationship (QSAR) study using Vlife molecular design suite (MDS) 2 software on various purine derivatives. These novels scaffolds/candidates, which could have the potential to inhibit 5FSO would represent promising starting points as lead compounds and certainly aid the experimental designing of anticancer drugs.Materials and Methods: Purine derivatives are studied and based on the QSAR study new structures are drawn and predicted the biological activity using the Vlife MDS Software-Module Name: QSAR Plus. Auto dock 1.2.6 software is a suite of automated docking tools. It is designed to predict how small molecules, such a substrate or drug candidates, bind to receptors of the known 3D structure. 5FSO protein preparation and optimization, ligand preparation and optimization, and docking simulations were carried out by using biological databases such as PubChem, Drug Bank, Protein Data Bank.Results: To estimate the activity, computational studies had been applied. In addition, the newly designed compound can be used as a scaffold to design more purine compounds which may be a potent inhibitor of 5FSO protein.Conclusion: The results depict as the newly designed molecules has better binding energy than standard drug and these compounds may possess better anticancer activity.

Serum allantoin and aminothiols as biomarkers of chronic heart failure

Background Oxidative stress (OS) represents the primary mediator of chronic heart failure (CHF) development and progression. It is well established that homocysteine is able to generate reactive oxygen species. Small amounts of allantoin in human serum result from free radical action on urate and may provide a stable marker for in vivo free radical activity.To investigate whether some easily measurable indexes such as antioxidants (uric acid, glutathione) and related molecules (allantoin, homocysteine and cysteine) can serve as OS biomarkers.Methods We investigated 75 stable CHF patients. Aminothiols and purine compound levels were determined by capillary electrophoresis.Results The homocysteine level was markedly elevated in CHF patients, whatever the aetiology. Parameters of the transsulfuration pathway and the investigated purine compounds were significantly increased. Conversely, total glutathione was decreased. The allantoin/uric acid ratio was significantly higher in CHF patients with an hyperhomocysteinaemia >17 μmol/L. All parameters of the transsulfuration and purine degadation pathways were significantly correlated, suggesting an OS in CHF patients.Conclusion Our data show an imbalance of serum aminothiols and purine compounds in these CHF patients on adapted therapy. We suggest that the evaluation and control of these new markers may help improve the OS that participates in the progression of the disease.