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Wyniki wyszukiwania dla: drug design
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Antibiotic resistance in Staphylococcus aureus strains isolated from cows with mastitis in the eastern Poland and analysis of susceptibility of resistant strains to alternative non-antibiotic agents: lysostaphin, nisin and polymyxin B.
PublikacjaThe aim of the studies was analysis of resistance of Staphylococcus aureus isolates from bovine mastitis in eastern part of Poland to a set of 20 antibiotics and three alternative agents: lysostaphin, nisin and polymyxin B. Eighty-six out of 123 examined isolates were susceptible to all of 20 tested antibiotics (70 %). The highest percentage of resistance was observed in the case of β-lactam antibiotics: amoxicillin (n=22, 17.9...
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Human UDP-Glucuronosyltransferases: Effects of altered expression in breast and pancreatic cancer cell lines.
PublikacjaIncreased aerobic glycolysis and de novo lipid biosynthesis are common characteristics of invasive cancers. UDP-glucuronosyltransferases (UGTs) are phase II drug metabolizing enzymes that in normal cells possess the ability to glucuronidate these lipids and speed their excretion; however, de-regulation of these enzymes in cancer cells can lead to an accumulation of bioactive lipids, which further fuels cancer progression. We hypothesize...
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Distinct cellular uptake patterns of two anticancer unsymmetrical bisacridines and their metabolic transformation in tumor cells.
PublikacjaUnsymmetrical bisacridines (UAs) represent a novel class of anticancer agents. Their high cytotoxicity towards multiple human cancer cell lines and inhibition of human tumor xenograft growth in nude mice signal their potential for cancer treatment. Therefore, the mechanism of their strong biological activity is broadly investigated. Here, we explore the efflux and metabolism of UAs, as both strongly contribute to the development...
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Modulation of UDP-glucuronidation by acridinone antitumor agents C-1305 and C-1311 in HepG2 and HT29 cell lines, despite slight impact in noncellular systems.
PublikacjaBackground Among the studied antitumor acridinone derivatives developed in our laboratory, 5-dimethylaminopropylamino-8-hydroxytriazoloacridinone (C-1305) and 5-diethylaminoethylamino-8-hydroxyimidazoacridinone (C-1311) exhibited cytotoxic and antitumor properties against several cancer types and were selected to be evaluated in preclinical and early-phase clinical trials. In the present work, we investigated the impact of C-1305...
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Gamma oscillations precede interictal epileptiform spikes in the seizure onset zone
PublikacjaOBJECTIVE: To investigate the generation, spectral characteristics, and potential clinical significance of brain activity preceding interictal epileptiform spike discharges (IEDs) recorded with intracranial EEG. METHODS: Seventeen adult patients with drug-resistant temporal lobe epilepsy were implanted with intracranial electrodes as part of their evaluation for epilepsy surgery. IEDs detected on clinical macro- and research microelectrodes...
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Synthesis, physicochemical and theoretical studies on new rhodium and ruthenium dimers. Relationship between structure and cytotoxic activity
PublikacjaTwo dimeric compounds of the general formulae (Et3NH)2[Rh2(μ2-L)4Cl2] (1) (where L = thiophene-2-carboxylate) and [((η6-p-cymene)Ru)2(μ-Cl)3]PF6 (2) have been synthesized using a new method. The unique anionic complex 1 (space group P bca) has octahedral coordination in which the equatorial positions are occupied by the oxygen atoms of four thiophene-2-carboxylates in a paddle wheel fashion. In complex 2 (space group ), each Ru(II)...
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Anticancer Properties of Amino Acid and Peptide Derivatives of Mycophenolic Acid
PublikacjaBackground: Although Mycophenolic Acid (MPA) is applied as prodrugs in clinic as an immunosuppressant, it also possesses anticancer activity. MPA acts as Inosine-5’-Monophosphate Dehydrogenase (IMPDH) inhibitor, where the carboxylic group at the end of the side chain interacts with Ser 276 of the enzyme via hydrogen bonds. Therefore, MPA derivatives with other polar groups indicated high inhibition too. On the other hand, potent...
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Application of BiOClnBrm photocatalyst to cytostatic drugs removal from water; mechanism and toxicity assessment
PublikacjaThe photocatalytic activity of series of BiOClnBrm photocatalysts toward degradation and mineralization of the cytostatic drugs 5-fluorouracil (5-FU) and imatinib mesylate (IMA) both singly and in their mixture under simulated solar and visible light irradiation has been investigated. Screening test revealed that among BiOClnBrm photocatalysts synthesized by a solvothermal method, the one with molar 1.3Cl/0.7Br ratio was the most...
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Development and validation of a GC–MS/MS method for the determination of 11 amphetamines and 34 synthetic cathinones in whole blood
PublikacjaPurpose Psychoactive compounds that contain a phenylethylamine structure (such as amphetamine-type stimulants and synthetic cathinones) are one of the major classes of stimulants on the recreational drug market. Approximately 670 new psychoactive substances (NPS) are monitored only in Europe; however, new psychoactive compounds are being developed for illicit trade each year. In this context, the development of new analytical procedures...
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Improved degradation of etodolac in the presence of core-shell ZnFe2O4/SiO2/TiO2 magnetic photocatalyst
PublikacjaIn the present study, susceptibility to photocatalytic degradation of etodolac, 1,8-diethyl-1,3,4,9 – tetrahydro pyran - [3,4-b] indole-1-acetic acid, which is a non-steroidal anti-inflammatory drug frequently detected in an aqueous environment, was for the first time investigated. The obtained p-type TiO2-based photocatalyst coupled with zinc ferrite nanoparticles in a core-shell structure improves the separation and recovery...
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Long-Term Stability of Benzodiazepines and Z-Hypnotic Drugs in Blood Samples Stored at Varying Temperatures
PublikacjaBenzodiazepines (BZDs) and Z-drugs are among the most commonly prescribed pharmaceuticals in the world and are considered standard care for various mental illnesses and for treatment of sleeping and anxiety disorders, alcohol withdrawal, muscle spasms and epilepsy. Some BZDs are not allowed as pharmaceuticals in many countries, and they are used as "designer benzodiazepines" (DBZDs). All these compounds are typically screened in...
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Fluconazole resistant Candida auris clinical isolates have increased levels of cell wall chitin and increased susceptibility to a glucosamine-6-phosphate synthase inhibitor
PublikacjaIn 2009 Candida auris was first isolated as fungal pathogen of human disease from ear canal of a patient in Japan. In less than a decade, this pathogen has rapidly spread around the world and has now become a major health challenge that is of particular concern because many strains are resistant to multiple class of antifungal drugs. The lack of available antifungals and rapid increase of this fungal pathogen provides an incentive...
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Role of miR-15b/16–2 cluster network in endometrial cancer: An in silico pathway and prognostic analysis
PublikacjaEndometrial cancer (EC) is the second most common cancer in women. A large number of human cancers exhibit dysregulation of microRNA expression including EC. MiR-15b/16–2 is one of the best-known miRNA clusters that is expressed in many types of cancer tissues. Herein, we analyzed the expression of individual miR-15b/16–2 cluster members, its paralogues, and their target network analysis, as well as their prognostic significance...
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Artificial intelligence for biomedical engineering of polysaccharides: A short overview.
PublikacjaThe advent of computer-aided concepts and cognitive algorithms, along with fuzzy sets and fuzzy logic thoughts, supported the idea of ‘making computers think like people’ (Lotfi A. Zadeh, IEEE Spectrum, 21 (26–32), 1984). Such a school of thought enabled the sophistication of mission-oriented...
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Tetracycline and ampicillin resistance of Escherichia coli strains of surface water origin: the potential for horizontal transfer of resistance genes = Oporność na tetracyklinę i ampicylinę szczepów Escherichia Coli wyizolowanych z wody powierzchniowej : możliwość horyzontalnego przenoszenia genów oporności
PublikacjaThe aim of this preliminary study was to assess the occurrence and molecular diversity of tetracycline and ampicillin resistance genes carried by Escherichia coli present in surface water. Bacterial strains were isolated from two watercourses (the Reda River and the Oliwski Stream) that influence the quality of coastal waters in the Gdańsk Bay (Northern Poland) by direct discharge. The bacterial drug susceptibility, tested against...
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Non-toxic fluorine-doped TiO2 nanocrystals from TiOF2 for facet-dependent naproxen degradation
PublikacjaIn the present study, the photocatalytic degradation of naproxen (NPX), which is a nonsteroidal anti-inflammatory drug (NSAID), frequently detected in drinking water, was investigated. The F-doped TiO2 with defined morphology was successfully obtained from TiOF2 and applied for photocatalytic degradation under UV-vis and visible light. All samples were characterised by X-ray diffraction, scanning electron microscopy, X-ray photoelectron...
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Assestment of the anti-cancer activity of the copper complexes with imidazole and pivalato ligands
PublikacjaDespite the development of science and technology progress so far there have not been found effective drugs for cancer. Many coordination compounds were investigated due to their antitumor potential. The most known cis-diamminedichloroplatinum(II) is used as anti-cancer therapeutic agent. The copper complexes are the coordination compounds possessing anti-tumour properties. Their capability to kill cancer cells is mainly linked...
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(4-(Bis(4-Fluorophenyl)Methyl)Piperazin-1-yl)(Cyclohexyl)Methanone Hydrochloride (LDK1229): A New Cannabinoid CB1 Receptor Inverse Agonist from the Class of Benzhydryl Piperazine Analogs
PublikacjaSome inverse agonists of cannabinoid receptor type 1 (CB1) have been demonstrated to be anorectic antiobesity drug candidates. However, the first generation of CB1 inverse agonists, represented by rimonabant (SR141716A), otenabant, and taranabant, are centrally active, with a high level of psychiatric side effects. Hence, the discovery of CB1 inverse agonists with a chemical scaffold distinct from these holds promise for developing...
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Dissecting gamma frequency activities during human memory processing
PublikacjaGamma frequency activity (30-150 Hz) is induced in cognitive tasks and is thought to reflect underlying neural processes. Gamma frequency activity can be recorded directly from the human brain using intracranial electrodes implanted in patients undergoing treatment for drug-resistant epilepsy. Previous studies have independently explored narrowband oscillations in the local field potential and broadband power increases. It is not...
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Electrochemical simulation of metabolic reduction and conjugation reactions of unsymmetrical bisacridine antitumor agents, C-2028 and C-2053
PublikacjaElectrochemistry (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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Effect of pH on optical sensing with poly-L-lysine-modified nanodiamonds
PublikacjaNitrogen-vacancy (NV) centers are crystallographic defects which provide diamonds with unique physical properties. The centers are known for their intensive, time-stable fluorescence, and an electron spin, which exhibits long coherence time and may be manipulated using external stimuli. Nanodiamonds containing the NV centers are promising tools in biolabeling, biosensing, and drug delivery due to the aforementioned properties of...
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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
PublikacjaA 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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Targeting of FLT3-ITD kinase contributes to high selectivity of imidazoacridinone C-1311 against FLT3-activated leukemia cells
PublikacjaDrugs targeting receptor tyrosine kinase FLT3 are of particular interest since activating FLT3-internal tandem duplication (ITD) mutations abundantly occur in fatal acute myeloid leukemias (AMLs). Imidazoacridinone C-1311, a DNA-reactive inhibitor of topoisomerase II, has been previously shown to be a potent and selective inhibitor of recombinant FLT3. Here, we expand those findings by studying its effect on leukemia cells with...
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The influence of food phytochemicals on cyclic phosphodiesterase 4 (PDE4) activity
PublikacjaCyclic phosphodiesterase 4 (PDE4) belongs to family of cyclic phosphodiesterases, which are expressed predominantly in inflammatory cells, airway smooth muscles, cardiovascular tissues and brain. Inhibitors of this family of enzymes found medicinal applications as antidepressants, antiinflamatory drugs (mainly in airway diseases) or antiasthmatics (Ibudilast). PDE4 inhibitors are also being tested for preventing the development...
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Prenatal exposure to substance of abuse: A worldwide problem
PublikacjaSubstance abuse during pregnancy is an important public health issue affecting the mother and the growing infant. Preterm labor, miscarriage, abruption and postpartum hemorrhage are obstetric complications which have been associated with women who are dependent on abused substances. Moreover, women are also at an increased risk of medical problems such as poor nutrition, anemia, urinary tract infections as well as sexually transmitted...
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Fatal N-Ethylhexedrone Intoxication
PublikacjaN-Ethylhexedrone [2-(ethyloamino)-1-phenylhexan-1-one; α-ethylaminohexanophenone; NEH] is one of the most recent synthetic cathinones that appeared on the illegal market in late 2015. The majority of information concerning the model of consumption of NEH and its impact on the body originates only from self-reports from grey literature websites and drug forums. There are only limited data associated with the concentrations of NEH...
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Antibiotic resistance, virulence, and phylogenetic analysis of Escherichia coli strains isolated from free-living birds in human habitats
PublikacjaWild birds can be colonized by bacteria, which are often resistant to antibiotics and have various virulence profiles. The aim of this study was to analyze antibiotic resistance mechanisms and virulence profiles in relation to the phylogenetic group of E. coli strains that were isolated from the GI tract of wildfowl. Out of 241 faecal samples, presence of E. coli resistant to a cephalosporin (ESBL/AmpC) was estimated for 33 isolates...
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Validation and modification of HPLC method for monitoring acetaminophen plasma concentrations in patients with chronic pancreatitis
PublikacjaBackground. Pancreatitis is the inflammation of the pancreas. The infl ammation may occur suddenly and resolve in a few days with the treatment in case of acute pancreatitis (AP). Chronic pancreatitis (CP) is a persistent inflammation of the pancreas that results in irreversible morphological changes and impairment of both exocrine and endocrine functions. Abdominal...
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Novel Resveratrol-Based Substrates for Human Hepatic, Renal, and Intestinal UDP-Glucuronosyltransferases
PublikacjaTrans-Resveratrol (tRes) has been shown to have powerful antioxidant, anti-inflammatory, anti-carcinogenic, and anti-aging properties; however, its use as a therapeutic agent is limited by its rapid metabolism into its conjugated forms by UDP-Glucuronosyltransferases (UGTs). The aim of the current study was to test the hypothesis that the limited bioavailability of tRes can be improved by modifying its structure to create analogs...
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The antitumor compound triazoloacridinone C-1305 inhibits FLT3 kinase activity and potentiates apoptosis in mutant FLT3-ITD leukemia cells.
PublikacjaAim: FMS-like receptor tyrosine kinase (FLT3) is expressed in some normal hematopoietic cell types and plays an important role in the pathogenesis of acute myeloid leukemia (AML). In this study, we examined the effects of triazoloacridinone C-1305, an antitumor compound, on AML cells with different FLT3 status in vitro. Methods: A panel of human leukemic cell lines with different FLT3 status was used, including FLT3 internal tandem...
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Indole-Acrylonitrile Derivatives as Potential Antitumor and Antimicrobial Agents—Synthesis, In Vitro and In Silico Studies
PublikacjaA series of 2-(1H-indol-2-yl)-3-acrylonitrile derivatives, 2a–x, 3, 4a–b, 5a–d, 6a–b, and 7, were synthesized as potential antitumor and antimicrobial agents. The structures of the prepared compounds were evaluated based on elemental analysis, IR, 1H- and 13NMR, as well as MS spectra. X-ray crystal analysis of the representative 2-(1H-indol-2-yl)-3-acrylonitrile 2l showed that the acrylonitrile double bond was Z-configured. All...
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Rapid and simple multi-analyte LC–MS/MS method for the determination of benzodiazepines and Z-hypnotic drugs in blood samples: Development, validation and application based on three years of toxicological analyses
PublikacjaBenzodiazepines (BZDs) and Z-drugs have been particularly important treatments for sleeping and anxiety disorders for many years. However, recently, a number of new benzodiazepines (named designer benzodiazepines, DBZDs) were synthesised, but some of them have never been used in the clinic; they reached the black drug market as new psychoactive substances and are used for recreational purposes. The abuse of these substances has...
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Electrophoretic Deposition of Chitosan/Eudragit E 100/AgNPs Coatings for Controlled Release of Antibacterial Substance
PublikacjaThe development of bacterial infection of the tissues surrounding an implant is one of the leading causes of implant surgery failure. In order to prevent the deposition of bacteria on the implant surface and the formation of biofilm, coatings that exhibit antibacterial properties are manufactured. However, the problem is the controlled release of the therapeutic substance from the coating over the extended life of the implant [1],...
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Analytical data on molecular umbrella: cispentacin and molecular umbrella: fluorescent probe conjugates
Dane BadawczeAnalytical data (NMR, MS, FTIR) for nine conjugates of molecular umbrella with cispentacin, Lys(Mca) or Nap-NH2. The conjugates have been rationally designed as potential antifungal agents. 1H NMR and 13C NMR spectra were obtained at 500 MHz Varian Unity Plus spectrometer and the deuterated solvents were used as internal locks. High-resolution mass...
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Chicken feather keratin as a source of bioactive peptides useful in prevention of metabolic disorders – in silico and in vitro hydrolysis
PublikacjaProtein derived bioactive peptides not only serve as nutrients but can also exert drug-like activity, e.g. antidiabetic, antihypertensive, or antimicrobial, to name a few. Most biopeptides have beneficial effects on health that make them attractive for nutraceutical applications. The majority of bioactive peptides have been obtained from food proteins, but protein-rich by-products generated by agriculture...
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Caffeine Inhibits Differentiation Of Lung Cancer Stem Cells By Modulating Their Respiratory Metabolism
PublikacjaIt is ell established that many tumor types contain a fraction of cells, with stem cell-like properties, called cancer stem cells (CSCs), that are resistant to apoptosis induced by therapeutic agents. The presence of CSCs may explain why a standard anticancer treatment, that eliminates only differentiated cancer cells, does not lead to cancer cure.We previously showed the existence of caffeine-sensitive mechanism that controls...
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A method for the production of D-tagatose using a recombinant Pichia pastoris strain secreting beta-D-galactosidase from Arthrobacter chlorophenolicus and a recombinant L-arabinose isomerase from Arthrobacter sp. 22c
PublikacjaD-Tagatose is a natural monosaccharide which can be used as a low-calorie sugar substitute in food, beverages and pharmaceutical products. It is also currently being tested as an anti-diabetic and obesity control drug. D-Tagatose is a rare sugar, but it can be manufactured by the chemical or enzymatic isomerization of D-galactose obtained by a beta-D-galactosidase-catalyzed hydrolysis of milk sugar lactose and the separation of...
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Development of Biocompatible Fe3O4@SiO2 Nanoparticles as Subcellular Delivery Platform for Glucosamine-6-phosphate Synthase Inhibitors
PublikacjaNumerous 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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Intermolecular Interactions of Edaravone in Aqueous Solutions of Ethaline and Glyceline Inferred from Experiments and Quantum Chemistry Computations
PublikacjaEdaravone, acting as a cerebral protective agent, is administered to treat acute brain infarction. Its poor solubility is addressed here by means of optimizing the composition of the aqueous choline chloride (ChCl)-based eutectic solvents prepared with ethylene glycol (EG) or glycerol (GL) in the three different designed solvents compositions. The slurry method was used for spectroscopic solubility determination in temperatures...
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Joanna Słabońska
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