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Wyniki wyszukiwania dla: drug design
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Molecular mechanism of proton-coupled ligand translocation by the bacterial efflux pump EmrE
PublikacjaThe current surge in bacterial multi-drug resistance (MDR) is one of the largest challenges to public health, threatening to render ineffective many therapies we rely on for treatment of serious infections. Understanding different factors that contribute to MDR is hence crucial from the global “one health” perspective. In this contribution, we focus on the prototypical broad-selectivity proton-coupled antiporter EmrE, one of the...
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Foliate-Targeting Quantum Dots-β-Cyclodextrin Nanocarrier for Efficient Delivery of Unsymmetrical Bisacridines to Lung and Prostate Cancer Cells
PublikacjaTargeted drug delivery by nanocarriers molecules can increase the efficiency of cancer treatment. One of the targeting ligands is folic acid (FA), which has a high affinity for the folic acid receptors, which are overexpressed in many cancers. Herein, we describe the preparation of the nanoconjugates containing quantum dots (QDs) and β-cyclodextrin (β-CD) with foliate-targeting properties for the delivery of anticancer compound...
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Natural Deep Eutectic Solvents as Agents for Improving Solubility, Stability and Delivery of Curcumin
PublikacjaPurpose Study on curcumin dissolved in natural deep eutectic solvents (NADES) was aimed at exploiting their beneficial properties as drug carriers. Methods The concentration of dissolved curcumin in NADES was measured. Simulated gastrointestinal fluids were used to determine the concentration of curcumin and quantum chemistry computations were performed for clarifying the origin of curcumin solubility enhancement in NADES. Results NADES...
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The Substantial Improvement of Amphotericin B Selective Toxicity Upon Modification of Mycosamine with Bulky Substituents
PublikacjaAbstract: Background: It is assumed that the unfavorable selective toxicity of an antifungal drug Amphotericin B (AmB) can be improved upon chemical modification of the antibiotic molecule. Objective: The aim of this study was verification of the hypothesis that introduction of bulky substituents at the amino sugar moiety of the antibiotic may result in diminishment of mammalian vitro toxicity of thus prepared AmB derivatives. Methods:...
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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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Evaluation of possibilities in identification and susceptibility testing for Candida glabrata clinical isolates with the Integral System Yeast Plus (ISYP)
PublikacjaThe aim of this study was to evaluate possibilities of correct identification and susceptibility testing of C. glabrata clinical isolates with Integral System Yeast Plus (ISYP). For species identification, as the reference method, API Candida test and species-specific PCR reactions were used. The potential of antifungal susceptibility testing by the ISYP test was compared with the Sensititre Yeast One. Whilst the reference methods...
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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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Imidazoacridinone-dependent lysosomal photodestruction: a pharmacological Trojan horse approach to eradicate multidrug-resistant cancers
PublikacjaMultidrug resistance (MDR) remains a primary hindrance to curative cancer therapy. Thus, introduction of novel strategies to overcome MDR is of paramount therapeutic significance. Sequestration of chemotherapeutics in lysosomes is an established mechanism of drug resistance. Here, we show that MDR cells display a marked increase in lysosome number. We further demonstrate that imidazoacridinones (IAs), which are cytotoxic fluorochromes,...
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Antifungal Activity of Capridine β as a Consequence of Its Biotransformation into Metabolite Affecting Yeast Topoisomerase II Activity
PublikacjaIn the last few years,increasing importance is attached to problems caused by fungal pathogens. Current methods of preventing fungal infections remain unsatisfactory. There are several antifungal compounds whichare highly effective in some cases, however, they have limitations in usage: Nephrotoxicity and other adverse effects. In addition, the frequent use of available fungistatic drugs promotes drug resistance....
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Nanoparticles: Taking a Unique Position in Medicine
PublikacjaThe human nature of curiosity, wonder, and ingenuity date back to the age of humankind. In parallel with our history of civilization, interest in scientific approaches to unravel mechanisms underlying natural phenomena has been developing. Recent years have witnessed unprecedented growth in research in the area of pharmaceuticals and medicine. The optimism that nanotechnology (NT) applied to medicine and drugs is taking serious...
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Organic solvents aggregating and shaping structural folding of protein, a case study of the protease enzyme
PublikacjaLow solubility of reactants or products in aqueous solutions can result in the enzymatic catalytic reactions that can occur in non-aqueous solutions. In current study we investigated aqueous solutions containing different organic solvents / deep eutectic solvents (DESs) that can influence the protease enzyme's activity, structural, and thermal stabilities. Retroviral aspartic protease enzyme is responsible for the cleavage of the...
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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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Effects of Addictive Substances During Pregnancy and Infancy and Their Analysis in Biological Materials
PublikacjaThe use of addictive substances during pregnancy is a serious social problem, not only because of effects on the health of the woman and child, but also because drug or alcohol dependency it detracts from childcare and enhances the prospect of child neglect and family breakdown. Developing additive substance abuse treatment programs for pregnant women is socially important and can help ensure the health of babies, prevent subsequent...
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Tailoring the electrochemical degradation of iron protected with polypyrrole films for biodegradable cardiovascular stents
PublikacjaThe degradation of polypyrrole (PPy) coated iron is studied in phosphate buffer saline solution at 37 °C by odd random phase multisine electrochemical impedance spectroscopy (ORP-EIS). PPy is electropolymerized with anti-inflammatory salicylates incorporated in the film, as a drug release system. The modelling of EIS over time provides the quantitative description of the corrosion behaviour of the material. Thus, the reliable...
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FLUID BED COATING OF MINITABLETS AND PELLETS WITH OPTIMIZATION OF THE PROCESS BASED ON TAGUCHI METHOD
PublikacjaSmall particles like pellets are coated in fluid bed systems. This method can be also feasible for minitablets but the selection of optimal process parameters is complicated. The aim of the research was to optimize the coating process for minitablets and to compare the conditions required for pellets. Minimum fluidization velocities (umf) for 2.0 and 2.5 mm minitablets and 0.7-0.8 mm or 1.0-1.25 mm pellets were determined experimentally....
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Synthesis and biological activity of ester derivatives of mycophenolic acid and acridines/acridones as potential immunosuppressive agents
PublikacjaImproved derivatives of mycophenolic acid (MPA) are necessary to reduce the frequency of adverse effects, this drug exerts in treated patients. In this study, MPA was coupled with N-(x-hydroxyalkyl)-9-acridone-4-carboxamides or N-(x-hydroxyalkyl)acridine-4-carboxamides to give respective ester conjugates upon Yamaguchi protocol. This esterification required protection of phenol group in MPA. Designed conjugates revealed higher...
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Activation Energy and Inclination Magnetic Dipole Influences on Carreau Nanofluid Flowing via Cylindrical Channel with an Infinite Shearing Rate
PublikacjaThe infinite shear viscosity model of Carreau fluid characterizes the attitude of fluid flow at a very high/very low shear rate. This model has the capacity for interpretation of fluid at both extreme levels, and an inclined magnetic dipole in fluid mechanics has its valuable applications such as magnetic drug engineering, cold treatments to destroy tumors, drug targeting, bio preservation, cryosurgery, astrophysics, reaction kinetics,...
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Intermolecular Interactions as a Measure of Dapsone Solubility in Neat Solvents and Binary Solvent Mixtures
PublikacjaDapsone is an effective antibacterial drug used to treat a variety of conditions. However, the aqueous solubility of this drug is limited, as is its permeability. This study expands the available solubility data pool for dapsone by measuring its solubility in several pure organic solvents: N-methyl-2-pyrrolidone (CAS: 872-50-4), dimethyl sulfoxide (CAS: 67-68-5), 4-formylmorpholine (CAS: 4394-85-8), tetraethylene pentamine (CAS:...
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Cell Density-Dependent Cytological Stage Profile and Its Application for a Screen of Cytostatic Agents Active Toward Leukemic Stem Cells
PublikacjaProliferation and expansion of leukemia is driven by leukemic stem cells (LSCs). Multidrug resistance (MDR) of LSCs is one of the main reasons of failure and relapses in acute myeloid leukemia (AML) treatment. In this study, we show that maintaining HL-60 at low cell culture density or applying a 240-day treatment with anthrapyridazone (BS-121) increased the percentage of primitive cells, which include LSCs determining the overall...
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Sustainable polymers targeted at the surgical and otolaryngological applications: Circularity and future
PublikacjaThe ongoing climate changes, high air and noise pollution have significant impact on humans’ health. This influence is especially visible in otolaryngology, which focuses on respiratory and hearing systems disfunctions. However, even though surgeries are done in response to diseases related to climate changes, they also have a negative impact on the environment, mostly connected with the inherence of single-use fossil fuel derived...
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Physical and Mechanical Evaluation of Silicone-Based Double-Layer Adhesive Patch Intended for Keloids and Scar Treatment Therapy
PublikacjaGrowing interest in silicone elastomers for pharmaceutical purposes is due to both theirbeneficial material effect for scar treatment and their potential as drug carriers. Regarding their morphological structure, silicone polymers possess unique properties, which enable a wide range of applicability possibilities. The present study focused on developing a double-layer adhesive silicone film (DLASil) by evaluating its physical...
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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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Phosphate and Thiophosphate Biphenyl Analogs as Steroid Sulfatase Inhibitors
PublikacjaIn the present work, we report convenient methods for the synthesis and biological evaluation of phosphate and thiophosphate biphenyl derivatives exhibiting steroid sulfatase (STS) activity. The described synthesis is based on straightforward preparation of biphenyl-4-ol and 40-hydroxybiphenyl- 4-carboxylic acid ethyl ester modified with various phosphate or thiophosphate moieties. The inhibitory effects of these compounds were...
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Influence of the addition of citric acid on the physico-chemical properties of poly(sorbitol sebacate-co- butylene sebacate)
PublikacjaThe article presents the results of the physicochemical properties of poly(sorbitol sebacate- co-butylene sebacate) (PSBS) obtained with 0.25; 0.5; 0.75; 1 mol of citric acid (KC). It was shown that PSBS obtained with 0.25 and 0.5 mol KC is characterized by the most optimal mechanical and thermal properties. As a result of the study, it was found that the use of sorbitol and citric acid allows obtaining ester materials with...
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The Metal-Free Regioselective Deuteration of 2-Methylquinolin-8-ol and 2,5-Dimethylquinolin-8-ol, Spectroscopic and Computational Studies
PublikacjaAbstract: Aim and Background: Introducing deuterium to a molecule is of interest to a wide variety of research, including investigation of reaction mechanisms or kinetics, analysis of drug metabolism, structural elucidation of molecules, and syntheses of isotopically labeled materials used for NMR spectroscopy and medicinal research. Objective: The transition-metal-free regioselective deuteration of 2-methylquinolin-8-ol...
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Imidazoacridinone antitumor agent C-1311 as a selective mechanism- based inactivator of human cytochrome P450 1A2 and 3A4 isoenzymes.
Publikacja5-Diethylaminoethylamino-8-hydroxyimidazoacridinone (C-1311), a promising antitumor agent that is also active against autoimmune diseases, was determined to be a selective inhibitor of the cytochrome P450 (CYP) 1A2 and 3A4 isoenzymes. Therefore, C-1311 might modulate the effectiveness of other drugs used in multidrug therapy. The present work aimed to identify the mechanism of the observed C-1311-mediated inactivation of CYP1A2...
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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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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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Optoelectronic investigation of nanodiamond interactions with human blood
PublikacjaWe present optoelectronic investigation of in vitro interactions of whole human blood with different nanodiamond biomarkers. Plasmo-chemical modifications of detonation nanodiamond particles gives the possibility for controlling their surface for biological applications. Optical investigations reveal the biological activity of nanodiamonds in blood dependent on its surface termination. We compare different types of nanodiamonds:...
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Molecular dynamics studies of polyurethane nanocomposite hydrogels
PublikacjaPolyurethane PEO-based hydrogels have a broad range of biomedical applicability. They are attractive for drug-controlled delivery systems, surgical implants and wound healing dressings. In this study, a PEO based polyurethane hydrogels containing Cloisite R 30B, an organically modified clay mineral, was synthesized. Structure of nanocomposite hydrogels was determined using XRD technique. Its molecular dynamics was studied by means...
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Determination of impurities in pharmaceutical products using LC-MS
PublikacjaPharmaceutical products can be contaminated by residues of solvents, reagents (used for the synthesis) or degradation products. Impurities in drug may pose a risk to human health and life, therefore analysis and identification of impurities in pharmaceutical products is veryimportant and inevitable.High performance liquid chromatography coupled with mass spectrometry (MS) is very useful technique for identification impurities in...
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Selected Methods for the Chemical Phosphorylation and Thiophosphorylation of Phenols
PublikacjaThis Focus Review gathers together a selection of methods for the chemical phosphorylation of phenols that employ three‐ and four‐coordinate phosphorus compounds. Phosphorylated scaffolds can exhibit enhanced properties compared to their non‐phosphorylated analogues, such as increased biological activity and increased/decreased solubility; as such, phosphorus compounds have gained more and more interest in organic and medicinal...
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Urinary Tract Infections Caused by K. pneumoniae in Kidney Transplant Recipients – Epidemiology, Virulence and Antibiotic Resistance
PublikacjaUrinary tract infections are the most common complication in kidney transplant recipients, possibly resulting in the deterioration of a long-term kidney allograft function and an increased risk of recipient’s death. K. pneumoniae has emerged as one of the most prevalent etiologic agents in the context of recurrent urinary tract infections, especially with multidrug resistant strains. This paper discusses the epidemiology and risk...
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Determination of Toxicological Parameters of Selected Bioactive Organic Chemicals Using the Ostracodtoxkit FTM
PublikacjaAssessment of the impact of pharmaceutical residues on living organisms is very complex subject. Apart from taking into account the toxicity of individual compounds also their presence in mixtures should be taken into account. In this work, attempts were made to assess the ecotoxicity of biologically active substances (with 50 % effective concentration (EC50) values growing from fluoxetine (EC50 = 4.431 nM) >> gemfibrozil ≈ 17α-ethinylestradiol...
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Antifungal dipeptides incorporating an inhibitor of homoserine dehydrogenase
PublikacjaThe antifungal activity of 5‐hydroxy‐4‐oxo‐L‐norvaline (HONV), exhibited under conditions mimicking human serum, may be improved upon incorporation of this amino acid into a dipeptide structure. Several HONV‐containing dipeptides inhibited growth of human pathogenic yeasts of the Candida genus in the RPMI‐1640 medium, with minimal inhibitory concentration values in the 32 to 64 μg mL−1 range. This activity was not affected by multidrug...
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Voriconazole-Based Salts Are Active against Multidrug-Resistant Human Pathogenic Yeasts
PublikacjaVoriconazole (VOR) hydrochloride is unequivocally converted into VOR lactates and valinates upon reaction with silver salts of organic acids. This study found that the anticandidal in vitro activity of these compounds was comparable or slightly better than that of VOR. The Candida albicans clinical isolate overexpressing CaCDR1/CaCDR2 genes, highly resistant to VOR, was apparently more susceptible to VOR salts. On the other hand,...
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Low frequency of itraconazole resistance found among avian Aspergillus fumigatus isolates
PublikacjaAspergillus fumigatus is the most frequent etiological factor of invasive aspergillosis in human as well as animals, including birds. Aspergillosis caused by drug-resistant strains poses a significant therapeutic issue, especially if resistance pattern includes insensitivity to triazoles, i.e. drugs recommended for the primary therapy purposes. Majority of resistant isolates hold the TR34/L98H...
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Application of bioassays in studies on the impact of pharmaceuticals on the environment
PublikacjaDrug interactions are often desirable particularly in medicine, when treatment of a patient requires using a mixture of drugs in specific doses to produce the adequate therapeutic effect. Unfortunately, interactions between drugs in the environment are not as desirable, despite the fact that drugs are present in the environment at low concentration levels [1]. Pharmaceuticals are present in the environment in a mixture of compounds,...
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Modulation of CYP3A4 activity and induction of apoptosis, necrosis and senescence by the antitumor imidazoacridinone C-1311 in human hepatoma cells
PublikacjaThere is increasing evidence that the expression level of drug metabolic enzymes affects the final cellular response following drug treatment. Moreover, anti-tumour agents may modulate enzymatic activity and/or cellular expression of metabolic enzymes in tumour cells. We investigated the influence of CYP3A4 overexpression on the cellular response induced by the anti-tumour agent C-1311 in hepatoma cells. C-1311-mediated CYP3A4...
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Development and evaluation of RADA-PDGF2 self-assembling peptide hydrogel for enhanced skin wound healing
PublikacjaBackground: Wound healing complications affect numerous patients each year, creating significant economic and medical challenges. Currently, available methods are not fully effective in the treatment of chronic or complicated wounds; thus, new methods are constantly sought. Our previous studies showed that a peptide designated as PDGF2 derived from PDGF-BB could be a promising drug candidate for wound treatment and that RADA16-I...
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VUV photofragmentation of the six-membered heterocyclic molecules containing oxygen
PublikacjaCancer is a significant public health concern worldwide, which results in millions of deaths each year. The standard cure routine for cancer is surgery, and nowadays, radiotherapy or a hadrontherapy. Depending on the type of cancer, patients may undergo additional treatment, including targeted therapy. A combination of radio- or hadron-therapy with proper drug treatment can inhibit the proliferation of cancer cells and thus can...
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Application of the near-infrared spectroscopy in the pharmaceutical technology
PublikacjaNear-infrared (NIR) spectroscopy is currently the fastest-growing and the most versatile analytical method not only in the pharmaceutical sciences but also in the industry. This review focuses on recent NIR applications in the pharmaceutical technology. This article covers monitoring, by NIR, of many manufacturing processes, such as granulation, mixing or drying, in order to determine the end-point of these processes. In this...
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Detection of some volatile degradation products released during photoexposition of ranitidine in a solid state
PublikacjaRanitidine (RAN) is on top of the list of prescribed drugs, due to its popularity as a selective H2-receptor antagonist, which efficiently decreases the amount of acid produced in the stomach. RAN is not stable both in a solid state and in a solution, which creates manufacturing problems, requires appropriate storage conditions, and results in a short drug shelf-life. The aim of this work was to study the emission of volatile...
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Application of vibrational spectroscopy, thermal analyses and X-Ray diffraction in the rapid evaluation of the stability in solid-state of ranitidine, famotidine and cimetidine
PublikacjaThis paper reports the study on applicability of Fourier transform infrared (FTIR), near-infrared (NIR) and Raman spectroscopy, differential scanning calorimetry (DSC) and X-ray diffraction (XRD) for the estimation of the chemical stability and photostability of histamine H2-receptor antagonist substances. Ranitidine hydrochloride (RAN), famotidine (FAM) and cimetidine (CIM) were tested and differences in sensitivity were measured...
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State of the art and prospects of methods for determination of lipophilicity of chemical compounds
PublikacjaLipophilicity of the compounds is useful to (i) explain their distribution in biological systems, which is different in plant and in animal organisms, (ii) predict the possible pathways of pollutant transport in the environment, and (iii) support drug discovery process and select optimal composition in terms of bioactivity and bioavailability. The lipophilic properties can be determined by two main approaches, experimental, which...
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Monosubstituted hydrazone β-cyclodextrin derivatives for pH-sensitive complex formation with aromatic drugs
PublikacjaA new and convenient synthetic pathway was developed to produce monosubstituted cyclodextrins with high yields. Each of the β-cyclodextrin derivatives described in this work has an aromatic substituent connected with cyclodextrin core by a pH-sensitive hydrazone linker and a carbon chain. Carbon chains differ in lengths having one or three carbon atoms. The correlation between water solubility and linker length was determined using...
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Novel steroid sulfatase inhibitors based on N ‐thiophosphorylated 3‐(4‐aminophenyl)‐coumarin‐7‐O‐sulfamates
PublikacjaIn the present work, we described convenient methods for the synthesis ofN-thiophosphorylated 3-(4-aminophenyl)-coumarin-7-O-sulfamates as steroid sulfatase(STS) inhibitors. To design the structures of the potential STS inhibitors, molecularmodeling techniques were used. A computational docking method was used to deter-mine the binding modes of the synthesized inhibitors as well as to identify potentialinteractions between specified...
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The Efficacious Benefit of 25-Hydroxy Vitamin D to Prevent COVID-19: An In-Silico Study Targeting SARS-CoV-2 Spike Protein
PublikacjaThe environment has rapidly looked at proven specialist task forces in the aftermath of the COVID-19 pandemic to build public health policies and measures to mitigate the effects of emerging coronaviruses. According to the researchers, taking 10 μg of 25-hydroxy vitamin D daily is recommended to keep us safe. There have been several studies recently indicating that there is a reduced risk of contracting Coronavirus by 25-hydroxy...
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Comparing the permeability of human and porcine small intestinal mucus for particle transport studies
PublikacjaThe gastrointestinal mucus layer represents the last barrier between ingested food or orally administered pharmaceuticals and the mucosal epithelium. This complex gel structure plays an important role in the process of small intestinal absorption. It provides protection against hazardous particles such as bacteria but allows the passage of nutrients and drug molecules towards the intestinal epithelium. In scientific research, mucus...
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Glucosinolates from lepidium peruvianum as potential antiamnestic drugs
PublikacjaLepidium peruvianum (maca) (Brassicaceae) is a naturally occurring plant mainly in the high Andes of Peru. In recent years, it has been intensively researched in terms of its influence on various diseases and towards health improvement. Alzheimer’s disease is an incurable disease that most often affects adults over the age of 60. As since 2003 the US Food and Drug Administration (FDA) did not approve any new drug for Alzheimer’s...