Search results for: DRUG DEVELOPMENT
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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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Antifungal Activity of Capridine β as a Consequence of Its Biotransformation into Metabolite Affecting Yeast Topoisomerase II Activity
PublicationIn 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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A Green Chemistry "environmentally friendly" approach to the synthesis of chloro-intermediates of ephedrine/pseudoephedrine
PublicationMethylamphetamine is an addictive stimulant drug that strongly activates certain systems in the brain. It is closely related chemically to amphetamine, but the central nervous system effects of methamphetamine are greater. There is much interest in methylamphetamine among scientists and therefore the synthesizes of methylamphetamine and its metabolites are carried out on a large scale in chemical laboratories. Globally, ephedrine...
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Xanthone synthetic derivatives with high anticandidal activity and positive mycostatic selectivity index values
PublicationWith the current massive increases in drug-resistant microbial infection as well as the significant role of fungal infections in the death toll of COVID-19, discovering new antifungals is extremely important. Natural and synthetic xanthones are promising derivatives, although only few reports have demonstrated their antifungal mechanism of action in detail. Newly synthetized by us xanthone derivative 44 exhibited strong antifungal...
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Ethylcellulose in Organic Solution or Aqueous Dispersion Form in Designing Taste-Masked Microparticles by the Spray Drying Technique with a Model Bitter Drug: Rupatadine Fumarate
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A.D.A.M. test (Antibiofilm Dressing's Activity Measurement) — Simple method for evaluating anti-biofilm activity of drug-saturated dressings against wound pathogens
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Distinction of clenbuterol intake from drug or contaminated food of animal origin in a controlled administration trial – the potential of enantiomeric separation for doping control analysis
PublicationThe differentiation of clenbuterol abuse and unintentional ingestion by contaminated meat is crucial with respect to the valuation of an adverse analytical finding in human sports doping control. The proportion of the two enantiomers of clenbuterol may serve as potential discriminating parameter. For the determination of the individual enantiomers, specific methods were developed and validated for the different matrices under investigation...
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The Product of Matrix Metalloproteinase Cleavage of Doxorubicin Conjugate for Anticancer Drug Delivery: Calorimetric, Spectroscopic, and Molecular Dynamics Studies on Peptide–Doxorubicin Binding to DNA
PublicationMatrix metalloproteinases (MMPs) are extracellular matrix degradation factors, promoting cancer progression. Hence, they could provide an enzyme-assisted delivery of doxorubicin (DOX) in cancer treatment. In the current study, the intercalation process of DOX and tetrapeptide-DOX, the product of the MMPs' cleavage of carrier-linked DOX, into dsDNA was investigated using stationary and time-resolved fluorescence spectroscopy, UV-Vis...
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Computational methods for calculation of binding free energy for ligand-receptor complexes
PublicationAccurate description of the molecular complexes energetic influence is required for understanding of many biological functions carried out by proteins. Therefore, estimation of binding free energy for ligand-receptor complexes is of highest importance for structure-based ligand design and drug discovery approaches.Experimental methods of determination of difference in Gibbs'es free energy have many limitations. Thus, computational...
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REVIEW OF CURRENT RESEARCH ON CHITOSAN AS A RAW MATERIAL IN THREE-DIMENSIONAL PRINTING TECHNOLOGY IN BIOMEDICAL APPLICATIONS
PublicationThree-dimensional (3D) biomaterial manufacturing strategies show an extraordinary driving force for the development of innovative solutions in the biomedical sector, including drug delivery systems, disease modelling and tissue and organ engineering. Due to its remarkable and promising biological and structural properties, chitosan has been widely studied for decades in several potential applications in the biomedical field. However,...
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Inhibitors of glucosamine-6-phosphate synthase as potential antimicrobials or antidiabetics – synthesis and properties
PublicationGlucosamine-6-phosphate synthase (GlcN-6-P synthase) is known as a promising target for antimicrobial agents and antidiabetics. Several compounds of natural or synthetic origin have been identified as inhibitors of this enzyme. This set comprises highly selective L-glutamine, amino sugar phosphate or transition state intermediate cis-enolamine analogues. Relatively low antimicrobial activity of these inhibitors, poorly penetrating...
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Metabolism of antitumour agent 1-nitroacridine derivative, C-1748 in pancreatic cancer cell lines
PublicationPancreatic 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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Bioprocess optimization using response surface methodology for production of the anticancer drug paclitaxel by Aspergillus fumigatus and Alternaria tenuissima: Enhanced production by ultraviolet and gamma irradiation
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High-Throughput Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry as an Alternative Approach to Monitoring Drug Resistance of Hepatitis B Virus
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The phenomenology, socio-demographic, and clinical profile of substance abusers admitted to drug de-addiction unit at eradah and mental health hospital, taif, Saudi Arabia
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Drug affinity to human serum albumin prediction by retention of cetyltrimethylammonium bromide pseudostationary phase in micellar electrokinetic chromatography and chemically advanced template search descriptors
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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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Specificity of Infant Digestive Conditions: Some Clues for Developing Relevant In Vitro Models
PublicationDigestion of nutrients is an essential function of the newborn infant gut to allow growth and development and understanding infant digestive function is essential to optimize nutrition and oral drug delivery. Ethical considerations prohibit invasive in vivo trials and as a consequence in vitro assays are often conducted. However, the choice of in vitro model parameters are not supported by an exhaustive analysis of the literature...
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Biomedical engineering of polysaccharide-based tissue adhesives: Recent advances and future direction
PublicationTissue adhesives have been widely used for preventing wound leaks, sever bleeding, as well as for enhancing drug delivery and biosensing. However, only a few among suggested platforms cover the circumstances required for high-adhesion strength and biocompatibility, without toxicity. Antibacterial properties, controllable degradation, encapsulation capacity, detectability by image-guided procedures and affordable price are also...
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Explicit solvent repulsive scaling replica exchange molecular dynamics ( RS‐REMD ) in molecular modeling of protein‐glycosaminoglycan complexes
PublicationGlycosaminoglcyans (GAGs), linear anionic periodic polysaccharides, are crucial for many biologically relevant functions in the extracellular matrix. By interacting with proteins GAGs mediate processes such as cancer development, cell proliferation and the onset of neurodegenerative diseases. Despite this eminent importance of GAGs, they still represent a limited focus for the computational community in comparison to other classes...
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The Effect of Millisecond Pulsed Electric Fields (msPEF) on Intracellular Drug Transport with Negatively Charged Large Nanocarriers Made of Solid Lipid Nanoparticles (SLN): In Vitro Study
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Antibiotic-Based Conjugates Containing Antimicrobial HLopt2 Peptide: Design, Synthesis, Antimicrobial and Cytotoxic Activities
PublicationRecent studies have shown that modified human lactoferrin 20−31 fragment, named HLopt2, possesses antibacterial and antifungal activity. Thus, we decided to synthesize and evaluate the biological activity of a series of conjugates based on this peptide and one of the antimicrobials with proven antibacterial (ciprofloxacin, CIP, and levofloxacin, LVX) or antifungal (fluconazole, FLC) activity. The drugs were covalently connected...
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Nowe substancje psychoaktywne. Cz. I. Współczesna sytuacja narkotykowa
PublicationGwałtowny wzrost liczby substancji wprowadzanych na rynek narkotykowy został zaobserwowany już pod koniec lat dziewięćdziesiątych XX wieku. Każdego roku syntezowane są nowe substancje jako analogi już istniejących, a ich ilość systematycznie rośnie. Niejednokrotnie wprowadzenie niewielkiej zmiany w strukturze związku może spowodować znaczne zmiany ich właściwości fizykochemicznych oraz psychoaktywnych. Nowe substancje psychoaktywne...
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Phage Therapy—Challenges, Opportunities and Future Prospects
PublicationThe increasing drug resistance of bacteria to commonly used antibiotics creates the need to search for and develop alternative forms of treatment. Phage therapy fits this trend perfectly. Phages that selectively infect and kill bacteria are often the only life-saving therapeutic option. Full legalization of this treatment method could help solve the problem of multidrug-resistant infectious diseases on a global scale. The aim of...
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TiO2-based magnetic nanocomposites with core-shell structure
PublicationThe main aim of the doctoral dissertation was preparation and characterization of photocatalysts, with particular emphasis on modified titanium (IV) oxide photocatalysts, which can be applied for the degradation of organic pollutants not susceptible to biodegradation. A particularly important aspect of the work was the development of preparation method of nanocomposites with the magnetic core-shell and photocatalyst shell (TiO2)...
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Experimental and Theoretical Screening for Green Solvents Improving Sulfamethizole Solubility
PublicationSolubility enhancement of poorly soluble active pharmaceutical ingredients is of crucial importance for drug development and processing. Extensive experimental screening is limited due to the vast number of potential solvent combinations. Hence, theoretical models can offer valuable hints for guiding experiments aimed at providing solubility data. In this paper, we explore the possibility of applying quantum-chemistry-derived...
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C-1311 (Symadex), a potential anti-cancer drug, intercalates into DNA between A and G moieties. NMR-derived and MD-refined stereostructure of the d(GAGGCCTC) 2 :C-1311 complex
PublicationImidazoacridinone C-1311 (Symadex®) is an antitumor agent which has been recommended for Phase II clinical trials a few years ago. Previously, it was shown experimentally that during the initial stage of its action C-1311 forms stable intercalation complexes with DNA duplexes. Herein, a NMR-derived stereostructure of d(GAGGCCTC)2:C-1311 complex was reported. The ligand was found locating itself between A and G moieties, forming...
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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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Cell Density-Dependent Cytological Stage Profile and Its Application for a Screen of Cytostatic Agents Active Toward Leukemic Stem Cells
PublicationProliferation 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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Glucosinolates from lepidium peruvianum as potential antiamnestic drugs
PublicationLepidium 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...
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Palindromic carbazole derivatives: unveiling their antiproliferative effect via topoisomerase II catalytic inhibition and apoptosis induction
PublicationHuman DNA topoisomerases are essential for crucial cellular processes, including DNA replication, transcription, chromatin condensation, and maintenance of its structure. One of the significant strategies employed in cancer treatment involves the inhibition of a specific type of topoisomerase, known as topoisomerase II (Topo II). Carbazole derivatives, recognised for their varied biological activities, have recently become a significant...
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Quantum dots conjugates with unsymmetrical bisacridines enhance cytotoxicity of these antitumor compounds in lung cancer cells and have protecting effects on normal cells
PublicationBackground: In recent years, with the rapid development of nanotechnology and its extensive applications in the medicine, nanocarriers for anticancer drug delivery have gained a great importance. Spherical semiconductor nanocrystals, frequently called quantum dots (QDs) are very attractive nanomaterials for bioimaging applications and they possess properties as potential candidates for drug carrier. Unsymmetrical bisacridines (UAs),...
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The Influence of Antitumor Unsymmetrical Bisacridines on 3D Cancer Spheroids Growth and Viability
PublicationThe culture of 3D spheroids is a promising tool in drug development and testing. Recently, we synthesized a new group of compounds, unsymmetrical bisacridines (UAs), which exhibit high cytotoxicity against various human cell lines and antitumor potency against several xenografts. Here, we describe the ability of four UAs—C-2028, C-2041, C-2045, and C-2053—to influence the growth of HCT116 and H460 spheres and the viability of HCT116...
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In vitro biological evaluation of a novel folic acid-targeted receptor quantum dot−β−cyclodextrin carrier for C-2028 unsymmetrical bisacridine in the treatment of human lung and prostate cancers
PublicationTraditional small-molecule chemotherapeutics usually do not distinguish tumors from healthy tissues. However, nanotechnology creates nanocarriers that selectively deliver drugs to their site of action. This work is the next step in the development of the quantum dot−β−cyclodextrin−folic acid (QD−β−CD−FA) platform for targeted and selected delivery of C−2028 unsymmetrical bisacridine in cancer therapy.Herein, we report an initial...
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Epigenetic inhibitor zebularine activates ear pinna wound closure in the mouse
PublicationBackground:Most studies on regenerative medicine focus on cell-based therapies and transplantations.Small-molecule therapeutics, though proved effective in different medical conditions, have not been extensivelyinvestigated in regenerative research. It is known that healing potential decreases with development and devel-opmental changes are driven by epigenetic mechanisms, which suggests epigenetic repression of regenerativecapacity.Methods:We...
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In vitro dissolution test of ketoprofene: development and evaluation of release from soft and hard gelatine capsules
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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
PublicationBenzodiazepines (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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DNA-damaging imidazoacridinone C-1311 induces autophagy followed by irreversible growth arrest and senescence in human lung cancer cells
PublicationImidazoacridinone 5-diethylaminoethylamino-8-hydroxyimidazoacridinone (C-1311) is an antitumor inhibitor of topoisomerase II and FMS-like tyrosine kinase 3 receptor. In this study, we describe the unique sequence of cellular responses to C-1311 in human non-small cell lung cancer (NSCLC) cell lines, A549 and H460. In A549 cells, C-1311 (IC80 = 0.08 µM) induced G1 and G2/M arrests, whereas H460 cells (IC80 = 0.051 µM) accumulated...
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Polysaccharide-based Nanocomposites for Biomedical Applications: A Critical Review
PublicationPolysaccharides (PSA) are taking specific position among biomaterials for advanced applications in medicine. Nevertheless, poor mechanical properties is known as the main drawback of PSA, which highlights need for PSA modification. Nanocomposites PSA (NPSA) are a class of biomaterials widely used as biomedical platforms, but despite their importance and worldwide use have not been reviewed. Herein we critically reviewed application...
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DEVELOPMENT OF HYDROGEL CAPSULES FOR USE IN DUAL-PHASE TOPICAL PREPARATIONS CONTAINING DIHYDROXYACETONE AND AMINO ACIDS – PRELIMINARY RESULTS
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Antitumor 1-nitroacridine derivative C-1748 induces significant apoptosis in pancreatic cancer cells.
PublicationPancreatic cancer is the fifth leading cause of cancer death and has the lowest survival rate of any solid cancer in the industrial countries. The poor prognosis of pancreatic cancer results from its tendency for late presentation, aggressive invasion, early metastasis, and resistance to chemotherapy. Gemcitabine still remains the best chemotherapeutic agent available for the treatment of advanced pancreatic cancer. However, gemcitabine...
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Essential Oils, Silver Nanoparticles and Propolis as Alternative Agents Against Fluconazole Resistant Candida albicans, Candida glabrata and Candida krusei Clinical Isolates
PublicationDevelopment of effective and safe therapeutic treatment of fungal infections remains one of the major challenge for modern medicine. The aim of presented investigation was to analyze the in vitro antifungal activity of selected essential oils, ethanolic extracts of propolis and silver nanoparticles dropped on TiO2 against azole-resistant C. albicans (n = 20), C. glabrata (n = 14) and C. krusei (n = 10) clinical isolates. Among...
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Human UDP-Glucuronosyltransferases: Effects of altered expression in breast and pancreatic cancer cell lines.
PublicationIncreased 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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Comparative molecular dynamics study of dimeric and monomeric forms of HIV-1 protease in ligand bound and unbound state
PublicationHuman immunodeficiency virus type 1 protease (HIV-1 PR) is a viral-encoded enzyme that forms a homodimer. HIV-1 PR is essential for replication and assembly of the virus and inactivation of HIV-1 PR enzyme causes production of immature, noninfectious viral particles and thus HIV-1 PR is an attractive target in anti-AIDS drug design. In our current work, we performed molecular dynamics (MD) calculations (500 ns) for two different...
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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
PublicationIn 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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Biofilm bakteryjny uropatogennych szczepów E. coli Dr+ jako czynnik indukujący przewlekłość zakażeń dróg moczowych ograniczający ich leczenie
PublicationZakażenia dróg moczowych (ZUM) stanowią jedne z najczęściej występujących infekcji bakteryjnych, dotykających każdego roku miliony osób na świecie. Problematyka tych zakażeń wynika z ich przewlekłości i nawrotów, pomimo stosowania terapii antybiotykowej oraz ciągle wzrastającej lekooporności uropatogenów je wywołujących. Dominującym czynnikiem etiologicznym ZUM są uropatogenne szczepy E. coli (UPECs), wykazujące zdolność do adhezji,...
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Biopsy needles coated with the antimicrobial coatings
PublicationDrug delivery systems are used to achieve higher therapeutic effects of medicaments in a specific diseased site with minimal toxicological effect. The used of biopolymers in drug delivery systems ensure the biocompatibility, biodegradability and low immunogenicity. Drug delivery systems enhance the drug delivery actively and can be used in different diseases. In this study, two types of polymer coatings were prepared and were...
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Assestment of the anti-cancer activity of the copper complexes with imidazole and pivalato ligands
PublicationDespite 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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Progress in ATRP-derived materials for biomedical applications
PublicationThe continuing wave of technological breakthroughs and advances is critical for engineering well- defined materials, particularly biomaterials, with tailored microstructure and properties. Over the last few decades, controlled radical polymerization (CRP) has become a very promising option for the synthesis of precise polymeric materials with an unprecedented degree of control over mo lecular architecture. Atom transfer radical...
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Prenatal exposure to substance of abuse: A worldwide problem
PublicationSubstance 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...