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Search results for: DRUG RESEARCH
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Self-Association of Amphotericin B: Spontaneous Formation of Molecular Structures Responsible for the Toxic Side Effects of the Antibiotic
PublicationAmphotericin B (AmB) is a lifesaving antibiotic used to treat deep-seated mycotic infections. Both the pharmaceutical activity and highly toxic side effects of the drug rely on its interaction with biomembranes, which is governed by the molecular organization of AmB. In the present work we present detailed analysis of self-assembly of AmB molecules in different environments, interesting from the physiological standpoint, based...
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Synthetic strategies in construction of organic macromolecular carrier–drug conjugates
PublicationMany metabolic inhibitors, considered potential antimicrobial or anticancer drug candidates, exhibit verylimited ability to cross the biological membranes of target cells. The restricted cellular penetration ofthose molecules is often due to their highhydrophilicity. One of the possible solutions to this problem is aconjugation of an inhibitor with a molecular organic nanocarrier. The conjugate thus formed should beable to penetrate...
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Determination of MDPBP in postmortem blood samples by gas chromatography coupled with mass spectrometry
PublicationMDPBP (1-(3,4-methylenedioxyphenyl)-2-(1-pyrrolidinyl)-1-butanone) is a new psychoactive substance sold on the black market. It has been a controlled drug of abuse in Poland and China since 2015 as some toxic and fatal cases connected with use of synthetic cathinone derivatives were observed. The fatal case outlined here concerns a 19 year-old man, who was found dead with an envelope containing white powder lying nearby the cadaver....
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Determination of bromhexine and its metabolites in equine serum samples by liquid chromatography – Tandem mass spectrometry: Applicability to the elimination study after single oral dose
PublicationBromhexine (BH), expectorant used in the treatment of respiratory disorders associated with viscid or excessive mucus, is not permitted for use in the competing horse by many authorities in horseracing and Olympic disciplines. Metabolic studies are of the great importance in anti-doping field because they allow for updating the selection of the most appropriate markers for prohibited substances, such as metabolites present at higher...
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Highly Conserved Homotrimer Cavity Formed by the SARS-CoV-2 Spike Glycoprotein: A Novel Binding Site
PublicationAn important stage in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) life cycle is the binding of the spike (S) protein to the angiotensin converting enzyme-2 (ACE2) host cell receptor. Therefore, to explore conserved features in spike protein dynamics and to identify potentially novel regions for drugging, we measured spike protein variability derived from 791 viral genomes and studied its properties by molecular...
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The role of intestine and liver in glucuronidation of the imidazo- and triazoloacridinone antitumor agents, C-1311 and C-1305: High affinity substrates for UGT1A10
PublicationCelem przeprowadzonych badań było określenie roli poszczególnych izoform UDP-glukuronylotransferazy (UGT)oraz mikrosomów jelita(HIM)i wątroby (HLM) wyizolowanych od różnych pacjentów w metabolizmie pochodnych akrydonu, związków C-1311 i C-1305. Wykazano, że rodziną UGT katalizującą przemiany C-1305 i C-1311 jest UGT1A, z najwyższą aktywnością wykazywaną przez pozawątrobowy izoenzym UGT1A10. Rozkład aktywności frakcji mikrosomalnych...
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Biotransformation of abused synthetic cannabinoids, JWH-018 and JWH-073, by human cytochromes P450 and UDP-glucuronosyltransferases
PublicationZwiązki oznaczone symbolami JWH-018 i JWH-073 są syntetycznymi pochodnymi kanabinoidów, obecnymi w preparatach o działaniu psychoaktywnym (K2/Spice). Wcześniejsze badań wykazały, że u osób przyjmujących tzw. ''legalną marihuanę'', głównymi produktami biotransformacji obecnymi w moczu były hydroksylowe pochodne obu związków, jak również ich glukuronidy. W związku z tym celem prowadzonych badań było określenie roli poszczególnych...
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The Imidazoacridinone Antitumor Drug, C-1311, Is Metabolized by Flavin Monooxygenases but Not by Cytochrome P450s.
PublicationPrezentowane w publikacji wyniki badań mają na celu wyjaśnienie roli enzymów wątrobowych w metabolizmie przeciwnowotworowych pochodnych C-1311 oraz C-1330. Oba związki inkubowane były z frakcją mikrosomalną oraz enzymami rekombinantowymi należącymi do grypy cytochromu P450, FMO oraz UGT. Badania wykazały, że oba związki są metabolizowane przez enzymy frakcji mikrosomalnej, ale nie przez enzymy cytochromu P450. Aktywność enzymatyczna...
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Role of Human UDP-Glucuronosyltransferases in the Biotransformation of the Triazoloacridinone and Imidazoacridinone Antitumor Agents C-1305 and C-1311 : Highly Selective Substrates for UGT1A10
Publication5-Diethylaminoethylamino-8-hydroxyimidazoacridinone, C-1311 (NSC-645809), is an antitumor agent shown to be effective against breast cancer in phase II clinical trials. A similar compound, 5-dimethylaminopropylamino-8-hydroxytriazoloacridinone, C-1305, shows high activity against experimental tumors and is expected to have even more beneficial pharmacological properties than C-1311. Previously published studies showed that these...
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Acridinone antitumor agents: C-1311, C-1330 and C-1305 are metabolized by flavin-containing monooxygenase isoenzymes: FMO1, FMO3 and FMO5 with different rates
PublicationRekombinantowe ludzkie monooksygenazy flawinowe: FMO1, FMO3, FMO5 indukują przemiany metaboliczne wybranych do badań pochodnych akrydonu. Biotransformacja związków C-1311, C-1330 i C-1305 przez FMO prowadzi do jednego produktu o strukturze N-tlenku. Wyniki badań wskazują, że najbardziej podatna na przemiany wobec FMO jest pochodna triazoloakrydonu C-1305. Wydaje się więc, że głównymi enzymami pierwszej fazy przemian metabolicznych...
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Protective Effect of Aronia Melanocarpa Polyphenols on Cadmium Accumulation in the Body: A Study in a Rat Model of Human Exposure to this Metal
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Aqueous Extracts of Selected Potentilla Species Modulate Biological Activity of Human Normal Colon Cells
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New Insights into Dietary Supplements Used in Sport: Active Substances, Pharmacological and Side Effects
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Antioxidants as a Potential Preventive and Therapeutic Strategy for Cadmium
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Prolonged Quercetin Administration Diminishes the Etoposide-Induced DNA Damage in Bone Marrow Cells of Rats
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Preliminary Study on the Antibacterial Activity of Essential Oils Alone and in Combination with Gentamicin Against Extended-Spectrum β-Lactamase-Producing and New Delhi Metallo-β-Lactamase-1-Producing Klebsiella pneumoniae Isolates
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Bacteriophage–Ciprofloxacin Combination Effectiveness Depends on Staphylococcus aureus–Candida albicans Dual-Species Communities’ Growth Model
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Biofilm Formation and Prevalence of Biofilm-Related Genes Among Clinical Strains of Multidrug-Resistant Staphylococcus aureus
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Environmental Phage-Based Cocktail and Antibiotic Combination Effects onAcinetobacter baumanniiBiofilm in a Human Urine Model
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The Effect of Subinhibitory Concentrations of trans-Anethole on Antibacterial and Antibiofilm Activity of Mupirocin Against Mupirocin-Resistant Staphylococcus aureus Strains
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Vitamin D Metabolism Gene Polymorphisms and Their Associated Disorders: A Literature Review
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Population analysis to assess the influence of age and body weight on pharmacokinetics and pharmacodynamics of dexmedetomidine in New Zealand White rabbits
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Acute and subacute (28-Day) toxicity studies of ionic liquid, didecyldimethyl ammonium acesulfamate, in rats
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The pharmacokinetics of propofol in ICU patients undergoing long-term sedation
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The quantification of reticulocyte maturation and neocytolysis in normal and erythropoietin stimulated rats
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Pharmacokinetics and pharmacodynamics of propofol and fentanyl in patients undergoing abdominal aortic surgery - a study of pharmacodynamic drug-drug interactions
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Disposition of Drugs of Abuse and Their Metabolites in Wastewater as a Method of the Estimation of Drug Consumption
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Rheological Characteristics of Novel Meloxicam-Loaded Complex Organogels Based on Fumed Silica and Poloxamer
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Current status of liposomal porphyrinoid photosensitizers
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Genetic Determinants of Vitamin D-Related Disorders; Focus on Vitamin D Receptor
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Morphine and methadone pre-exposures differently modify brain regional Fos protein expression and locomotor activity responses to morphine challenge in the rat
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<p>Potential effects of microbial air quality on the number of new cases of diabetes type 1 in children in two regions of Poland: a pilot study</p>
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Potential of Liquid Biopsy in Papillary Thyroid Carcinoma in Context of miRNA, BRAF and p53 Mutation
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Complexation of Bioelements and Toxic Metals by Polyphenolic Compounds - Implications for Health
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Genotoxicity of selected pharmaceuticals, their binary mixtures, and varying environmental conditions – study with human adenocarcinoma cancer HT29 cell line
PublicationPharmaceutical residues are present in the environment in mixtures and their adverse effects may also result from interactions that occur between compounds. Studies presented in this work focus on genotoxicity of pharmaceuticals from different therapeutic groups in mixtures and in individual solutions impacted with different environmental conditions assessed using comet assay (alkaline approach). Binary mixtures of pharmaceuticals...
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Targeting shelterin proteins for cancer therapy.
PublicationAs a global health challenge, cancer prompts continuous exploration for innovative therapies that are also based on new targets. One promising avenue is targeting the shelterin protein complex, a safeguard for telomeres crucial in preventing DNA damage. The role of shelterin in modulating ataxia- telangiectasia mutated (ATM) and ataxia-telangiectasia and Rad3-related (ATR) kinases, key players in the DNA damage response (DDR),...
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Low-Barrier Hydrogen Bond Determines Target-Binding Affinity and Specificity of the Antitubercular Drug Bedaquiline
PublicationThe role of short strong hydrogen bonds (SSHB) in ligand-target binding remains largely unexplored, thereby hin- dering a potentially important avenue in the rational drug de- sign. Here, we investigate the interaction between bedaquiline (Bq), a potent anti-tuberculosis drug, and the mycobacterial ATP synthase, to unravel the role of a specific hydrogen bond to a conserved acidic residue in the target affinity and specificity....
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Halgurd Nadhim Mohammed
PeopleI hold a master's degree in medical biology from Van Yüzüncü Yıl University- Turkey in 2017. I received a bachelor's degree in biology at Kirkuk University in 2011.I am a head of the Anesthesia department and lecturer at the Pharmacy Department at Kurdistan Technical Institute- Sulaimani, which is a private institute affiliated with the Ministry of higher education and Scientific Research of Kurdistan Region- Iraq. Recently, I...
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Problem of aggregation in dye-DNA interaction, calorimetry studies
PublicationNucleic acids are the biological target for many antimicrobial, antitumor and antiviral drugs. Ligand-DNA interactions can be classified into two major categories: 1. covalent binding, which can provide to intermolecular adducts, 2. physico-chemical interactions, which can be divided into intercalation (e.g. adriamycin) or groove binding (e.g. dystamycin). There are several methods to investigate interactions between drug and DNA....
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Determination of the chemical structure of potential organic impurities occurring in drug substance opipramol
PublicationThe tricyclic antipsychotic and antidepressant drug opipramol (opipramole) was examined with regard to the chemical structure of its organic impurities. Impurities were isolated from the technical product by chromatographic methods and their chemical structures were established by 1H NMR, MS and FTIR and further confirmed by comparison with commercially available products or with products obtained by independent synthesis, and...
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Ipertrofan Revisited—The Proposal of the Complete Stereochemistry of Mepartricin A and B
PublicationBeing a methyl ester of partricin, the mepartricin complex is the active substance of a drug called Ipertrofan (Tricandil), which was proven to be useful in treatment of benign prostatic hyperplasia and chronic nonbacterial prostatitis/chronic pelvic pain syndrome. Nevertheless, no direct structural evidence on the stereochemistry of its components has been presented to date. In this contribution, we have conducted detailed, NMR-driven...
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Data regarding a new, vector-enzymatic DNA fragment amplification-expression technology for the construction of artificial, concatemeric DNA, RNA and proteins, as well as biological effects of selected polypeptides obtained using this method
PublicationApplications of bioactive peptides and polypeptides are emerging in areas such as drug development and drug delivery systems. These compounds are bioactive, biocompatible and represent a wide range of chemical properties, enabling further adjustments of obtained biomaterials. However, delivering large quantities of peptide derivatives is still challenging. Several methods have been developed for the production of concatemers –...
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Impact of inorganic ions and pH variations on toxicity and endocrine potential of selected environmentally relevant pharmaceuticals
PublicationAssessment of the impact of pharmaceutical residues on living organisms is a very complex subject. Apart from taking into account the toxicity of individual compounds, environmental factors should also be taken into account. In this paper, attempts were made to assess the impact of coexisting inorganic ions and changes in pH on the toxicity of ten selected pharmaceuticals. Two bioassays were used to measure the estrogenic and androgenic...
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New Unsymmetrical Bisacridine Derivatives Noncovalently Attached to Quaternary Quantum Dots Improve Cancer Therapy by Enhancing Cytotoxicity toward Cancer Cells and Protecting Normal Cells
PublicationThe use of nanoparticles for the controlled drug delivery to cells has emerged as a good alternative to traditional systemic delivery. Quantum dots (QDs) offer potentially invaluable societal benefits such as drug targeting and in vivo biomedical imaging. In contrast, QDs may also pose risks to human health and the environment under certain conditions. Here, we demonstrated that unique combination of nanocrystals core components...
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Detection of propofol concentrations in blood by Raman spectroscopy
PublicationIn this paper we present a proof-of-concept of a Raman spectroscopy-based approach for measuring the content of propofol, a common anesthesia drug, in whole human blood, and plasma, which is intended for use during clinical procedures. This method utilizes the Raman spectroscopy as a chemically–sensitive method for qualitative detection of the presence of a drug and a quantitative determination of its concentration. A number of...
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Glutathione-mediated conjugation of anticancer drugs: an overview of reaction mechanisms and biological significance for drug detoxification and bioactivation.
PublicationThe effectiveness of many anticancer drugs depends on the creation of specific metabolites that may alter their therapeutic or toxic properties. One significant route of biotransformation is a conjugation of electrophilic compounds with reduced glutathione, which can be non-enzymatic and/or catalyzed by glutathione-dependent enzymes. Glutathione usually combines with anticancer drugs and/or their metabolites to form more polar...
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Factors causing degradation of sulfadimetoxine
PublicationSulfadimetoxine is a representative of sulfonamide drugs which presence inhibits growth of activated sludge bacteria, rhat is necessary for the effective mineralization of organic and inorganic contaminants. Therefore factors which con prevent this situation are searched. Aim of this study is selection of conditions causing efficien degradation of the drug- sulfadimetoxine. The impact of such aspects as : the type of oxidizing...
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Mechanism-based inactivation of human cytochrome P450 1A2 and 3A4 isoenzymes by antitumor triazoloacridinone C-1305.
Publication5-Dimethylaminopropylamino-8-hydroxytriazoloacridinone, C-1305, is a promising antitumor therapeutic agent with high activity against several experimental tumors. It was determined to be a potent and selective inhibitor of liver microsomal and human recombinant cytochrome P450 (CYP) 1A2 and 3A4 isoenzymes. Therefore, C-1305 might modulate the effectiveness of other drugs used in multidrug therapy. The objective of this study was...
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Thermodynamics and kinetics of amphotericin B self-association in aqueous solution characterized in molecular detail
PublicationAmphotericin B (AmB) is a potent but toxic drug commonly used to treat systemic mycoses. Its efficiency as a therapeutic agent depends on its ability to discriminate between mammalian and fungal cell membranes. The association of AmB monomers in an aqueous environment plays an important role in drug selectivity, as oligomers formed prior to membrane insertion – presumably dimers – are believed to act differently on fungal (ergosterol-rich)...
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Nanosize effect of clay mineral nanoparticles on the drug diffusion processes in polyurethane nanocomposite hydrogels
PublicationStudies of swelling and release of naproxen sodium (NAP) solution by polyurethane nanocomposite hydrogels containing Cloisite® 30B (organically modified montmorillonite (OMMT)) have been performed. Polyurethane nanocomposite hydrogels are hybrid, nontoxic biomaterials with unique swelling and release properties in comparison with unmodified hydrogels. These features enable to use nanocomposite hydrogels as a modern wound dressing....