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Search results for: IN VITRO METABOLISM
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New Chalcones Derivatives With Potent Antitumor Activity And Their Metabolism In Vitro
PublicationChalcone derivatives exhibit a broad range of biological activities, with antioxidant and cytotoxic properties among the most studied. Despite numerous reports on chalcones as cytotoxic, and potentially anticancer agents, very little is know on their actual mechanism of activity. Generally, chalcones are considered as antimitotic agents, which interfere with tubulin assembly.We have recently developed a new class of chalcones with...
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Characterization of In Vitro and In Vivo Metabolism of Antazoline Using Liquid Chromatography-Tandem Mass Spectrometry
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Systemy ekspresyjne białek cytochromu P450 w badaniach in vitro metabolizmu leków = Expression systems of cytochrome P450 proteins in studies of drug metabolism in vitro
PublicationBiałka cytochromu P450 to najważniejsze enzymy biorące udział w metabolizmie większości stosowanych w klinice leków, odpowiedzialne za ich aktywację lub detoksykację. Niektóre z dróg metabolizmu leku mogą być jednak odpowiedzialne za jego podwyższoną toksyczność. Nowe systemy ekspresyjne białek cytochromu P450 w komórkach ssaków, w tym człowieka, projektowane są w celu poznania roli metabolizmu w mechanizmie działania potencjalnych,...
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Amino acids metabolism and degradation is regulated during porcine oviductal epithelial cells (OECs) primary culture in vitro – a signaling pathways activation approach
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Electrochemical simulation of metabolism for antitumor-active imidazoacridinone C-1311 and in silico prediction of drug metabolic reactions
PublicationThe 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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Electrochemistry meets enzymes: Investigation of the biotransformation pathway of C-1311 based on electrochemical simulation in comparison to in vitro methods.
PublicationThe 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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Transcriptional activity of epigenetic remodeling genes declines in keratinocytes after in vitro expansion
PublicationPURPOSE: In vitro expansion is an invaluable method to obtain keratinocytes in amounts necessary for effective transplantation therapies. In vitro cell culturing provokes questions concerning potential epigenetic alterations occurring in expanded cells in the context of usefulness for transplantation and safety. The purpose of this study was to investigate as to whether keratinocyte expansion is associated with changes in the activity...
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Antiproliferative, Antiangiogenic, and Antimetastatic Therapy Response by Mangiferin in a Syngeneic Immunocompetent Colorectal Cancer Mouse Model Involves Changes in Mitochondrial Energy Metabolism
PublicationIn spite of the current advances and achievements in cancer treatments, colorectal cancer (CRC) persists as one of the most prevalent and deadly tumor types in both men and women worldwide. Drug resistance, adverse side effects and high rate of angiogenesis, metastasis and tumor relapse remain one of the greatest challenges in long-term management of CRC and urges need for new leads of anticancer drugs. We demonstrate that CRC...
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Electrochemical simulation of enzymatic transformations studied for the selected antitumor acridine derivatives
PublicationThe 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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The II phase metabolism of endogenous and exogenous compounds, including antitumor chemotherapeutics
PublicationThe II phase metabolism, it is a set of metabolism and excretion pathways of endogenous as well as exogenous compounds including xenobiotics. UDP-glucuronyltransferases (UGTs; EC 2.4.1.17) are the most crucial representatives of II phase enzymes, which are responsible for the transformation of bilirubine and bile acids, steroids and thyroid hormones and lipids. Exogenous compounds, including drugs, carcinogens, environmental pollutants...
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Prediction of Overall In Vitro Microsomal Stability of Drug Candidates Based on Molecular Modeling and Support Vector Machines. Case Study of Novel Arylpiperazines Derivatives
PublicationOther than efficacy of interaction with the molecular target, metabolic stability is the primary factor responsible for the failure or success of a compound in the drug development pipeline. The ideal drug candidate should be stable enough to reach its therapeutic site of action. Despite many recent excellent achievements in the field of computational methods supporting drug metabolism studies, a well-recognized procedure to model...
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Oxylipin profiling for clinical research: Current status and future perspectives
PublicationOxylipins are potent lipid mediators with increasing interest in clinical research. They are usually measured in systemic circulation and can provide a wealth of information regarding key biological processes such as inflammation, vascular tone, or blood coagulation. Although procedures still require harmonization to generate comparable oxylipin datasets, performing comprehensive profiling of circulating oxylipins in large studies...
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Detoxification of the tricyclic antidepressant opipramol and its analog – IS-noh by UGT enzymes before and after activation by phase I enzymes in rat liver microsomes
PublicationThe present studies were carried out to evaluate the simultaneous one-pot metabolism of opipramol (IS-opi) and analog (IS-noh) by phase I and phase II enzymes present in rat liver microsomes (RLM) as an alternative to separate testing with recombinant enzymes. This approach allows for more time-saving and cost-effective screening of the metabolism of newly discovered drugs. We also considered that the lack of results for phase...
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Metabolic Profiles of New Unsymmetrical Bisacridine Antitumor Agents in Electrochemical and Enzymatic Noncellular Systems and in Tumor Cells
PublicationNew unsymmetrical bisacridines (UAs) demonstrated high activity not only against a set of tumor cell lines but also against human tumor xenografts in nude mice. Representative UA compounds, named C-2028, C-2045 and C-2053, were characterized in respect to their physicochemical properties and the following studies aimed to elucidate the role of metabolic transformations in UAs action. We demonstrated with phase I and phase II enzymes...
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Electrochemical simulation of metabolic reduction and conjugation reactions of unsymmetrical bisacridine antitumor agents, C-2028 and C-2053
PublicationElectrochemistry (EC) coupled with analysis techniques such as liquid chromatography (LC) and mass spectrometry (MS) has been developed as a powerful tool for drug metabolism simulation. The application of EC in metabolic studies is particularly favourable due to the low matrix contribution compared to in vitro or in vivo biological models. In this paper, the EC(/LC)/MS system was applied to simulate phase I metabolism of the representative...
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Versatility of putative aromatic aminotransferases from Candida albicans.
PublicationAmino acids constitute the key sources of nitrogen for growth of Candida albicans. In order to survive inside the host in different and rapidly changing environments, this fungus must be able to adapt via its expression of genes for amino acid metabolism. We analysed the ARO8, ARO9, YER152C, and BNA3 genes with regards to their role in the nutritional flexibility of C. albicans. CaAro8p is undoubtedly the most versatile enzyme...
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Novel fused pyran derivatives induce apoptosis and target cell cycle progression in anticancer efficacy against multiple cell lines.
PublicationNitrogen-based heterocycles such as pyrazole, imidazole, 1,2,4-triazole, benzimidazole, and benzotriazole substituted fused pyran derivatives (6a–e, 8a–e, 10a–e, 12a–e,&14a–e) have been synthesized and tested for their in vitro anticancer efficacies against MCF7, A549, and HCT116 cancer cell lines. Among the compounds, 6e, 14b, and 8c were identified as the most potent against MCF7, A549, and HCT116, with IC50 values of 12.46 2.72...
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Nutritional and Pharmaceutical Properties of Bioactive Compounds in Organic and Conventional Growing Kiwifruit
PublicationThe bioactivity of two kiwifruit’s cultivars growing under organic and conventional conditions were studied and compared. The bioactive compounds were extracted with water and ethanol using similar conditions which are applied in pharmaceutical applications and for daily fruit consumption such as tea drink. Antioxidant radical scavenging assays [ferric-reducing/antioxidant power (FRAP); cupric reducing antioxidant capacity (CUPRAC);...
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Diamond Nanofilm Normalizes Proliferation and Metabolism in Liver Cancer Cells
PublicationPurpose: Surgical resection of hepatocellular carcinoma can be associated with recurrence resulting from the degeneration of residual volume of the liver. The objective was to assess the possibility of using a biocompatible nanofilm, made of a colloid of diamond nanoparticles (nfND), to fill the side after tumour resection and optimize its contact with proliferating liver cells, minimizing their cancerous transformation. Methods:...
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NUTRITIONAL AND PHARMACEUTICAL APPLICATIONS OF BIOACTIVE COMPOUNDS IN TROPICAL FRUITS
PublicationDuring the past two decades our international scientific group investigated in vitro the physicochemical and nutritional characteristics of some cultivars of durian at various stages of ripening, mangosteen and new cultivars of snake fruit in comparison with widely used avocado, kiwifruit and mango, and in vivo their influence on laboratory animals. The main objective of the present study was to screen and compare the properties...
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Mass spectrometry based identification of geometric isomers during metabolic stability study of a new cytotoxic sulfonamide derivatives supported by quantitative structure-retention relationships
PublicationA set of 15 new sulphonamide derivatives, presenting antitumor activity have been subjected to a metabolic stability study. The results showed that besides products of biotransformation, some additional peaks occurred in chromatograms. Tandem mass spectrometry revealed the same mass and fragmentation pathway, suggesting that geometric isomerization occurred. Thus, to support this hypothesis, quantitative structure-retention relationships...
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In Vitro and In Vivo Imaging-Based Evaluation of Doxorubicin Anticancer Treatment in Combination with the Herbal Medicine Black Cohosh
PublicationAs a substitution for hormone replacement therapy, many breast cancer patients use black cohosh (BC) extracts in combination with doxorubicin (DOX)-based chemotherapy. In this study, we evaluated the viability and survival of BC- and DOX-treated MCF-7 cells. A preclinical model of MCF-7 xenografts was used to determine the influence of BC and DOX administration on tumor growth and metabolism. The number of apoptotic cells after...
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Insulin-like growth factor type 2 is better than insulin-like growth factor type 1 a survival marker in patients after acute decompensation of heart failure
PublicationIntroduction:A decreased IGF-1 has been found in heart failure (HF). There are no reports assessing IGF-2 in HF, although in vitro study has shown, that IGF-2 stimulates cardiomyocyte proliferation more than IGF-1. The study aim was to compare the IGF-1 and IGF-2 concentration depending on HF exacerbation and annual survival.Material and methods:Among 75 patients hospitalized...
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In vitro enzyme kinetics and NMR-based product elucidation for glutathione S-conjugation of the anticancer unsymmetrical bisacridine C-2028 in liver microsomes and cytosol: major role of glutathione S-transferase M1-1 isoenzyme
PublicationThis work is the next step in studying the interplay between C-2028 (anticancer-active unsymmetrical bisacridine developed in our group) and the glutathione S-transferase/glutathione (GST/GSH) system. Here, we analyzed the concentration- and pH-dependent GSH conjugation of C-2028 in rat liver microsomes and cytosol. We also applied three recombinant human GST isoenzymes, which altered expression was found in various tumors. The...
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Development of Biocompatible Fe3O4@SiO2 Nanoparticles as Subcellular Delivery Platform for Glucosamine-6-phosphate Synthase Inhibitors
PublicationNumerous inhibitors of glucoseamine-6-phophate synthase (GlcN-6-P), the enzyme responsible from catalysis of the first step of metabolic pathway leading to metabolism 5’-diphospho-N-acetyl-D- glucosamine, were reported as effective agents for inhibiting the growth of various fungal pathogens. Among the reported inhibitors,...
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Metabolic transformations of antitumor imidazoacridinone, C-1311, with microsomal fractions of rat and human liver
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Przemiany metaboliczne in vitro niesymetrycznych bisakrydyn w układach bezkomórkowych i w komórkach nowotworowych oraz określenie wpływu tych pochodnych na aktywność enzymów metabolizujących leki
PublicationPrzedmiotem badań prowadzonych w ramach niniejszej pracy doktorskiej są cztery niesymetryczne bisakrydyny: C-2028, C-2041, C-2045 i C-2053, wykazujące wysoką aktywność cytotoksyczną [Konopa i in. 2019]. Otrzymane wyniki wskazały, że każdy z pierścieni (imidazoakrydonu i 1-nitroakrydyny) obecny w strukturze badanych związków odgrywa inną rolę w wykazywanych przez nie właściwościach fizykochemicznych i biologicznych. Właściwości...
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Phase I and phase II metabolism simulation of antitumor-active 2-hydroxyacridinone with electrochemistry coupled on-line with mass spectrometry.
PublicationHere, 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...