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Wyniki wyszukiwania dla: REACTIVE METABOLITE
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Electrochemical simulation of metabolism for antitumor-active imidazoacridinone C-1311 and in silico prediction of drug metabolic reactions
PublikacjaThe metabolism of antitumor-active 5-diethylaminoethylamino-8-hydroxyimidazoacridinone (C-1311) has been investigated widely over the last decade but some aspects of molecular mechanisms of its metabolic transformation are still not explained. In the current work, we have reported a direct and rapid analytical tool for better prediction of C-1311 metabolism which is based on electrochemistry (EC) coupled on-line with electrospray...
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Reactive metabolites of acridinone antitumor agents, C-1311 and C-1305, are trapped within the active site of CYP1A2 and CYP3A4, causing irreversible enzymes inactivation
PublikacjaZwiązki C-1305 i C-1311, zsyntetyzowane w Katedrze Technologii Leków i Biochemii, wykazują najsilniejsze właściwości przeciwnowotworowe wśród pochodnych, odpowiednio, triazolo- i imidazoakrydonu. Obecnie prowadzone są badania mające na celu określenie biochemicznego mechanizmu działania, jak również potencjalnych szlaków biotransformacji C-1305 i C-1311.W bieżącym etapie podjęto próbę określenia mechanizmu obserwowanej inhibicji...
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Phase I and phase II metabolism simulation of antitumor-active 2-hydroxyacridinone with electrochemistry coupled on-line with mass spectrometry.
PublikacjaHere, we report the metabolic profile and the results of associated metabolic studies of 2-hydroxyacridinone (2-OH-AC), the reference compound for antitumor-active imidazo- and triazoloacridinones. Electrochemistry coupled with mass spectrometry was applied to simulate the general oxidative metabolism of 2-OH-AC for the first time. The reactivity of 2-OH-AC products to biomolecules was also examined. The usefulness of the electrochemistry...
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Platelets in fetal growth restriction: role of reactive oxygen species, oxygen metabolism, and aggregation.
PublikacjaFetal growth restriction (FGR) is mainly caused by failure of the uteroplacental unit. Theexact pathogenesis remains unclear. The cause is thought to be related to abnormal platelet activation,which may...
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Urine metabolic fingerprinting using LC–MS and GC–MS reveals metabolite changes in prostate cancer: A pilot study
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Knowledge sharing in manufacturing subsidiaries: proactive and reactive perspective in knowledge exploitation context
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Diminshed toxicity of C-1748, 4-methyl-9-hydroxyethylamino-1-nitroacridine, compared with its demethyl analog, C-857, corresponds to its resistance to metabolism in HepG2 cells
PublikacjaThe narrow "therapeutic window" of anti-tumour therapy may be the result of drug metabolism leading to the activation or detoxification of antitumour agents. The aim of this work is to examine (i) whether the diminished toxicity of a potent antitumour drug, C-1748, 9-(2'-hydroxyethylamino)-4-methyl-1-nitroacridine, compared with its 4-demethyl analogue, C-857, results from the differences between the metabolic pathways for the...
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Genetic response to metabolic fluctuations: correlation between central carbon metabolism and DNA replication in Escherichia coli
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New plasma preparation approach to enrich metabolome coverage in untargeted metabolomics: plasma protein bound hydrophobic metabolite release with proteinase K
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Electrochemistry/mass spectrometry (EC/MS) for fast generation and identification of novel reactive metabolites of two unsymmetrical bisacridines with anticancer activity.
PublikacjaThe development of a new drug requires knowledge about its metabolic fate in a living organism, regarding the comprehensive assessment of both drug therapeutic activity and toxicity profiles. Electrochemistry (EC) coupled with mass spectrometry (MS) is an efficient tool for predicting the phase I metabolism of redox-sensitive drugs. In particular, EC/MS represents a clear advantage for the generation of reactive drug transformation...
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The production and properties of the secondary metabolites in selected car-nivorous plants = Produkcja i właściwości metabolitów wtórnych wybranych roślin owadożernych
PublikacjaPięć gatunków roślin owadożernych (Drosera aliciae, D. capensis, D. ramenta-cea, D. rotundifolia oraz Sarracenia psittacina ) zostało zbadanych pod ką-tem produkcji i właściwości metabolitów wtórnych między innymi flawonoidów inaftochinonów. W tym celu rośliny poddano elicytacji in vitro przy użyciuelicytorów abiotycznych - TYTANIT, kwas jasmonowy, BION oraz biotycznych -chityna i Enterobacter sakazaki. Badane związki ekstrahowano...
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Electrochemical simulation of enzymatic transformations studied for the selected antitumor acridine derivatives
PublikacjaThe elucidation of the metabolic pathways and the biotransformation mechanisms of potential drugs is a crucial point in drug development. It allows to know the activation routes of the new biologically active compounds, especially in respect to their possible toxicity. Generally, in vivo or in vitro experiments with liver microsomes or hepatocytes are performed. However, these testing schemes are tedious, time consuming and of...
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Human red blood cells targeted metabolome analysis of glycolysis cycle metabolites by capillary electrophoresis using an indirect photometric detection method
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Electrochemical and in silico approaches for liver metabolic oxidation of antitumor-active triazoloacridinone C -1305
Publikacja5-Dimethylaminopropylamino-8-hydroxytriazoloacridinone (C-1305) is a promising antitumor compound developed in our laboratory. A better understanding of its metabolic transformations is still needed to explain the multidirectional mechanism of pharmacological action of triazoloacridinone derivatives at all. Thus, the aim of the current work was to predict oxidative pathways of C-1305 that would reflect its phase I metabolism. The...
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Metabolism of 1α-hydroxyvitamin D3 by cytochrome P450scc to biologically active 1α,20-dihydroxyvitamin D3
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Antimicrobial and conformational studies of the active and inactive analogues of the protegrin-1 peptide
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Metabolism of chemical carcinogens
PublikacjaW rozdziale omówiono szlaki przemian metabolicznych wielu grup związków rakotwórczych z uwzględnieniem zarówno reakcji aktywacji jak i detoksykacji. SzczegÓlną uwagę poświęcono związkom rakotwórczym występującym w żywności.
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3-Methoxytyramine Is the Major Metabolite of Released Dopamine in the Rat Frontal Cortex: Reassessment of the Effects of Antipsychotics on the Dynamics of Dopamine Release and Metabolism in the Frontal Cortex, Nucleus Accumbens, and Striatum by a Simple T
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Oxygen evolution reaction on MoS2/C rods—robust and highly active electrocatalyst
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Metabolic response of cornflower (Centaurea cyanus L.) exposed to tribenuron-methyl: one of the active substances of sulfonylurea herbicides
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Secondary metabolites from Potentilla argentea
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Secondary metabolites of Rubus caesius (Rosaceae)
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Electrochemistry meets enzymes: Investigation of the biotransformation pathway of C-1311 based on electrochemical simulation in comparison to in vitro methods.
PublikacjaThe knowledge of the metabolic pathways and the biotransformation of new drugs is one of the major challenges in pharmaceutical research. It is crucial for elucidation of degradation routes of the new biologically active compounds, especially in the area of possible toxicity. Conventional in vitro drug metabolism studies are based on incubating drug candidate with e.g. hepatocytes or, most importantly, liver cell microsomes and...
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Differentiating between Inactive and Active States of Rhodopsin by Atomic Force Microscopy in Native Membranes
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Elimination of excretion of ibuprofen and its metabolites in horses
PublikacjaAnalytical procedure based on application of gas chromatography-mass spectrometry (GC-MS) at the step of detection, identification and quantitation of ibuprofen (IBU) and detection of its metabolites – 1-hydroxyibuprofen (1-OH IBU) and carboxyibuprofen (CBX IBU) in horse urine by selected ion monitoring mode after sample preparation covering extraction at pH 3-4 and methylation has been used. The ions at m/z 161, 220 (methylated...
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Compensation of supply current harmonics, reactive power, and unbalanced load current balance in the closed-loop control of a shunt active power filter
PublikacjaThis paper presents the compensation tasks performed by a shunt active power filter, including compensation of harmonic currents, reactive power, and an unbalanced load current. The paper demonstrates novel control of the shunt active power filter in a closed-loop system. The control algorithm was verified by performing simulations and compared the simulated results with those obtained in an open-loop control system. All simulations...
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Completing Autophagy: Formation and Degradation of the Autophagic Body and Metabolite Salvage in Plants
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Metabolism of antitumour agent 1-nitroacridine derivative, C-1748 in pancreatic cancer cell lines
PublikacjaPancreatic cancer has the highest mortality rate of all major cancers because of limited treatment options. Surgical removal of the tumour is possible only in its early stage, nevertheless the asymptomatic development very often makes unable an accurate diagnose. In the case of metastatic pancreatic cancer only chemotherapy, mainly with gemcitabine, can be offered to patients. However, common resistance towards gemcitabine imposes...
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Metabolic syndrome: a psychiatric outlook
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CYP3A4-dependent cellular response does not relate to CYP3A4-catalysed metabolites of C-1748 and C-1305 acridine antitumor agents in HepG2 cells
PublikacjaHigh CYP3A4 expression sensitizes tumor cells to certain antitumor agents while for others it can lower their therapeutic ef fi cacy. We have elucidated the in fl uence of CYP3A4 overexpression on the cellular response induced by antitumor acridine derivatives, C-1305 and C-1748, in two hepatocellular carcinoma (HepG2) cell lines, Hep3A4 stably transfected with CYP3A4 isoenzyme, and HepC34 expressing empty vector. The compounds...
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Proposed Amendments to Reactive Energy Billing
PublikacjaThis paper describes possible amendments to the rules of reactive energy billing in the tariffs in Poland. Modifications in the tariffs to improve their motivational function for distribution system users are identified as the most expedient. New problems arising from distributed generator operations are also indicated. A billing method that can be effectively implemented at the occurrence of distorted voltage and current waveforms...
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Updates in the Metabolism of Lactic Acid Bacteria
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Melatonin in the skin: synthesis, metabolism and functions
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Aberrations in Lipid Expression and Metabolism in Psoriasis
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The Influence of Hydrodynamic Conditions in a Laboratory-Scale Bioreactor on Pseudomonas aeruginosa Metabolite Production
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Reaction Model Taking into Account the Catalyst Morphology and Its Active Specific Surface in the Process of Catalytic Ammonia Decomposition
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Hyperproteic diet modifies microbiota composition and associated metabolites in rats
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Analytical procedures for determination of cocaine and its metabolites in biological samples
PublikacjaThe dangerous effects and increased usage of illicit drugs have inspired the development of analytical methodologies. We based our review of analytical procedures for determination of cocaine (COC) and its metabolites on literature from the past two decades. Our main aim was to compare the capabilities of different analytical techniques. The diversity of matrices from which COC is determined (e.g., blood, hair, saliva, plasma,...
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Characterization of metabolites in different kiwifruit varieties by NMR and fluorescence spectroscopy
PublikacjaIt is known from our previous studies that kiwifruits, which are used in common human diet, have preventive properties of coronary artery disease. This study describes a combination of 1H NMR spectroscopy, multivariate data analyses and fluorescence measurements in differentiating of some kiwifruit varieties, their quenching and antioxidant properties. A total of 41 metabolites were identified by comparing with literature data...
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Microbiota-derived metabolites in colorectal cancer patients in preoperative period
PublikacjaShort-chain fat-ty acids (SCFAs) are microbial derived metabo-lites, which have multiple beneficial properties. The amount of SCFAs depends on several fac-tors, such as age, diet (mainly intake of dietary fiber), and overall health condition. The normal proportion between SCFAs is 3:1:1 for acetate, proprionate and butyrate, respectively. In col-orectal cancer (CRC) patients, microbiota alter-ations have been shown. Consequently,...
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Novel insights into conjugation of antitumor-active unsymmetrical bisacridine C-2028 with glutathione: characteristics of non-enzymatic and glutathione S-transferase-mediated reactions
PublikacjaUnsymmetrical bisacridines (UAs) are a novel potent class of antitumor-active therapeutics. A significant route of phase II drug metabolism is conjugation with glutathione (GSH), which can be non-enzymatic and/or catalyzed by GSH-dependent enzymes. The aim of this work was to investigate the GSH-mediated metabolic pathway of a representative UA, C 2028. GSH supplemented incubations of C-2028 with rat, but not with human, liver...
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Health economy of the metabolic syndrome pandemic
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Reactive Processing and Functionalization of Ground Tire Rubber
PublikacjaThe dynamic development of the automotive industry resulted in a sig- nificant increase in rubber wastes, especially end-of-life tires, which are a serious threat to the natural environment and human health. This situation has enforced the industry and academic research groups to search new and cost-effective methods for recycling waste tires. In this field of research, reactive processing and functionaliza- tion seem to be a...
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In-Situ Processing of Biocomposites via Reactive Extrusion
PublikacjaLaw regulations, economic and environmental factors are the main causes for the rapidly growing interests in biocomposites’ research, conducted currently in a number of academic and industrial scientific centers. However, weak polymer matrix/filler interactions, common in biocomposites, result in unsatisfactory mechanical properties, which limit their practical applications. From many attempts performed to solve this problem, in-situ...
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Reactive Energy Billing in Operator Tariffs in Poland
PublikacjaThe paper describes the current method of reactive energy billing in the tariffs of distribution grid operators in Poland. The current solutions are subject to critical assessment. Issues related to the motivation effect of the current solutions on consumers are analysed. Problems that occur in relation with connecting distributed generators to the distribution grid and challenges related to prosumer billing are indicated.
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The Large Customer Reactive Power Control Possibilities
Publikacjan this paper the authors wish to draw attention to the rationale for, and the possibility of, the use of local reactive power sources by the Transmission Node Master Controller (TNMC). Large Customers (LC) are one of the possible reactive power sources. The paper presents the issues related to the need for coordination between the control systems installed in the LC network, and coordination between control systems of the LC as...
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Altered levels of nucleoside metabolite profiles in urogenital tract cancer measured by capillary electrophoresis
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Paraffin-Embedded Tissue as a Novel Matrix in Metabolomics Study: Optimization of Metabolite Extraction Method
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Active Site Architecture and Reaction Mechanism Determination of Cold Adapted beta-D-galactosidase from Arthrobacter sp. 32cB
PublikacjaArthbetaDG is a dimeric, cold-adapted beta-D-galactosidase that exhibits high hydrolytic and transglycosylation activity. A series of crystal structures of its wild form, as well as its ArthbetaDG_E441Q mutein complexes with ligands were obtained in order to describe the mode of its action. The ArthbetaDG_E441Q mutein is an inactive form of the enzyme designed to enable observation of enzyme interaction with its substrate. The...
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Structure of solvation water around the active and inactive regions of a type III antifreeze protein and its mutants of lowered activity
PublikacjaWater molecules from the solvation shell of the ice-binding surface are considered important for the antifreeze proteins to perform their function properly. Herein, we discuss the problem whether the extent of changes of the mean properties of solvation water can be connected with the antifreeze activity of the protein. To this aim, the structure of solvation water of a type III antifreeze protein from Macrozoarces americanus (eel...