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Department of Pharmaceutical Technology and Biochemistry
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total: 637
Catalog Publications
Year 2014
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The II phase metabolism of endogenous and exogenous compounds, including antitumor chemotherapeutics
PublicationThe II phase metabolism, it is a set of metabolism and excretion pathways of endogenous as well as exogenous compounds including xenobiotics. UDP-glucuronyltransferases (UGTs; EC 2.4.1.17) are the most crucial representatives of II phase enzymes, which are responsible for the transformation of bilirubine and bile acids, steroids and thyroid hormones and lipids. Exogenous compounds, including drugs, carcinogens, environmental pollutants...
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Wpływ kolejności dozowania surowców oraz sił ścinających na właściwości mieszanin polietylen dużej gęstości/miał gumowy, wytwarzanych przy użyciu współbieżnej wytłaczarki dwuślimakowej
PublicationKompozycje termoplastyczne polietylenu dużej gęstości (PE-HD) z udziałem 50 % mas. miału gumowego (GTR), wytwarzano przy użyciu współbieżnej wytłaczarki dwuślimakowej. Scharakteryzowano wpływ kolejności dozowania surowców oraz sił ścinających generowanych podczas intensywnego mieszania na parametry pracy wytłaczarki, wartości masowego wskaźnika szybkości płynięcia, statyczne właściwości mechaniczne (wytrzymałość na rozciąganie,...
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Zastosowanie bakteriocyn - peptydów o aktywności bakteriobójczej
PublicationBakteriocyny są to peptydy bakteriobójcze produkowane przez wiele rodzajów bakterii w celu eliminacji ze środowiska bakterii innych rodzajów lub konkurowania z nimi. Cechą charakterystyczną tych peptydów jest to, że są one syntetyzowane na rybosomach. Mogą być modyfikowane potranslacyjnie lub nie. W chwili obecnej bakteriocyny stosowane są w przemyśle spożywczym jako dodatek do produktów żywnościowych, jednak ich potencjał aplikacyjny...
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Związki endokrynne w środowisku. Problemy i wyzwania cz. I Emisja i los środowiskowy
PublicationWzrost świadomości dotyczącej niekorzystnego wpływu działalności człowieka na stan środowiska oraz dynamiczny rozwój technik analitycznych spowodował, że w ostatnich latach wzrosło zainteresowanie problematyką związków zakłócających prawidłowe funkcjonowanie układu endokrynnego. W opracowaniu zamieszczono informacje o niektórych związkach z grupy estrogenów, ich losie środowiskowym oraz oddziaływaniu na organizmy żywe.
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Związki endokrynne w środowisku. Problemy i wyzwania cz. II Wykrywanie i oznaczanie związków endokrynnych i/lub endokrynności próbek
PublicationOdkrycie istnienia w środowisku mikrozanieczyszczeń, do których należą między innymi związki z grupy EDC, spowodowało konieczność opracowania i wdrożenia nowych metod do praktyki analitycznej. Jedną z nich są nabierające coraz większego znaczenia techniki immunoanalizy. Mimo, iż nie są one rozwiązaniem nowym, ponieważ od dawna z powodzeniem stosuje się je w analizie klinicznej, mają wiele zalet pozwalających na wykorzystanie...
Year 2013
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99mTc-Galacto-RGD2: A Novel 99mTc-Labeled Cyclic RGD Peptide Dimer Useful for Tumor Imaging
PublicationThis study sought to evaluate [99mTc(HYNIC-Galacto-RGD2)-(tricine)(TPPTS)] (99mTc-Galacto-RGD2: HYNIC = 6-hydrazinonicotinyl; Galacto-RGD2 = Glu[cyclo[Arg-Gly-Asp-D-Phe-Lys(SAA-PEG2-(1,2,3-triazole)-1-yl-4-ethylamide)]]2 (SAA = 7-amino-L-glycero-L-galacto-2,6-anhydro-7-eoxyheptanamide, and PEG2 = 3,6-dioxaoctanoic acid); and TPPTS = trisodium triphenylphosphine-3,3',3''-trisulfonate) as a new radiotracer for tumor imaging. Galacto-RGD2...
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alfa-Aminotransferaza kwasu L-alfa-aminoadypinowego z Candida albicans jako cel molekularny
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Bacteriophages as an antistaphylococcal agent
PublicationRecently observed increase of infection caused by Staphylococcus aureus is currently one of the most important problem of clinical microbiology. Most of the strains responsible for the infections are a MRSA (methicillin resistant Staphylococcus aureus) strains. In this situation commonly used antibiotics are not sufficient. There is an urgent need to search for a new nonatibiotic treatment against this pathogen. In the literature...
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Biofilm formation and its regulation in Staphylococcus aureus
PublicationInfections caused by the major human and animal pathogen, Staphylococcus aureus are becoming an important problem due to its emerging resistance mechanisms and variety of virulence factors. Biofilm formation is considered to be one of the most important factor attributed to high pathogenicity of S. aureus. Described in the literature methods used in identification of biofilm forming abilities of bacteria consist of phenotypic and...
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Copper(II) complexes with substituted imidazole and chlorido ligands: X-ray, UV-Vis, magnetic and EPR studies and chemotherapeutic potential
PublicationCrystal structures, UV-Vis and EPR spectra and magnetic properties of four copper(II) complexes with chloride anions and 4-methylimidazole, 2-ethylimidazole, 2-isopropylimidazole or 2-ethyl-4-methylimidazole are described. In the solid state three of the complexes are mononuclear and one complex with 2-ethylimidazole is binuclear with bridging chlorido ions. UV-Vis spectra of the methanolic solutions of the complexes show LMCT...
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CYP3A4 overexpressin enhances the cytotoxicity of the antitumor triazoloacridinone derivative C-1305 in CHO cells
PublicationW pracy badano wpływ nadekspresji izoenzymu CYP3A4 na cytotoksyczność i odpowiedź komórkową indukowaną przez przeciwnowotworową pochodną triazoloakrydonu w modelowym układzie komórek CHO: dzikego typu, z nadekspresją reduktazy cytochromu P450 (CHO-HR) oraz z koekspresją reduktazy i izoenzymu CYP3A4 (CHO-HR-3A4). Wykazano, że komórki CHO wykazywały różną wrażliwość na badany związek, a linia CHO-HR okazała się najbardziej wrażliwa,...
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Dehydrogenaza sacharopiny (NADP+, tworząca L-glutaminian) z Candida albicans jako cel molekularny
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Desensitization of glucosamine-6-phosphate synthase to inhibition by UDP-GlcNAc
PublicationGlucosamine-6-phosphate (GlcN-6-P) synthase, known also as L-Glutamine: D-fructose-6-phosphate amidotransferase, catalyzes the first committed step in the pathway leading to the ultimate formation of UDP-GlcNAc. The final product of this pathway is an activated precursor of numerous macromolecules containing amino sugars, including chitin and mannproteins in fungi, peptidoglycan and lipopolysaccharides in bacteria, and glycoproteins...
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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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Evaluation of possibilities of genotyping of Candida glabrata clinical isolates with RAPD-PCR method and microsatellite analysis
PublicationThe aim of the study was to compare the discriminatory power of RAPD-PCR method using RSD10 primer and microsatellite (GACA)4 analysis for genotyping clinical isolates of C. glabrata. Isolates were received from patients of two Polish hospitals: Children's Memorial Health Institute in Warsaw (n=17) and Medical University of Gdansk (n=37). Species identification was confirmed by two phenotypic methods: growth on chromagar plates...
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Flavonoids from Pseudotsuga menziesii
PublicationFour O-acetylated flavonol glycosides, new in the plant kingdom, were isolated from the needles of Pseudotsuga menziesii. Their structures were established by 1D and 2D NMR and MS data.
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Genotyping of clinical isolates of fluconazole-resistant Candida albicans
PublicationThe aim of the study was to compare the discriminatory power of RAPD-PCR method with using RSD10 primer and microsatellite analysis with using (GACA)4 primer for genotyping clinical isolates of fluconazole-resistant C. albicans. Isolates were received from patients of Children's Memorial Health Institute in Warsaw. However in the case of both tested methods low number of amplified fragments was generated, nine and six different...
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Homoisocitrate dehydrogenase from Candida albicans: properties, inhibition, and targeting by an antifungal pro-drug
PublicationThe LYS12 gene from Candida albicans, coding for homoisocitrate dehydrogenase was cloned and expressed as a His-tagged protein in Escherichia coli. The purified gene product catalyzes the Mg2+- and K+-dependent oxidative decarboxylation of homoisocitrate to alpha-ketoadipate. The recombinant enzyme demonstrates strict specificity for homoisocitrate. SDS-PAGE of CaHIcDH revealed its molecular mass of 42.6±1 kDa, while in size-exclusion...
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Inhibition of T-type calcium channel disrupts Akt signaling and promotes apoptosis in glioblastoma cells.
PublicationGlioblastoma multiforme (GBM) are brain tumors that are exceptionally resitant to both radio- and chemotherapy regimens and novel approaches to treatment are needed. T-type calcium channels are one type of low voltage-gated channel (LVCC) involved in embryonic cell proliferation and differentiation; however they are often over-expressed in tumors, including GBM. In this study, we found that inhibition of T-type Ca channels in GBM...
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Isolation of xanthone and benzophenone derivatives from Cyclopia genistoides (L.) Vent. (honeybush) and their pro-apoptotic activity on synoviocytes from patients with rheumatoid arthritis
PublicationA fast and efficient method for the isolation of the C-glucosidated xanthones mangiferin and isomangiferin from the South-African plant Cyclopia genistoides was developed for the first time. Two benzophenone derivatives: 3-C-β-glucosides of maclurin and iriflophenone, were isolated from C. genistoides extracts using semi-preparative. The structures of the compounds were determined by 1D and 2D NMR experiments and/or LC-DAD-ESI–MS.
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Metabolic transformation of antitumor acridinone C-1305 but not C-1311 via selective cellular expression of UGT1A10 increases cytotoxic response: implications for clinical use.
PublicationThe acridinone derivates C-1305 and C-1311 are promising antitumor agents with high activity against several experimental cellular and tumor models and which are under evaluation in pre-clinical and early phase clinical trials. Recent evidence from our laboratories has indicated that both compounds were conjugated by several UGT isoforms with the most active being extrahepatic UGT1A10. The present studies were designed to test...
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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
PublicationThere 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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Możliwości wykorzystania bakteriocyn i olejków eterycznych jako nieantybiotykowych chemoterapeutyków przeciwgronkowcowych
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Peptydy przeciwgrzybowe
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Pregnane X receptor dependent up-regulation of CYP2C9 and CYP3A4 in tumor cells by antitumor acridine agents, C-1748 and C-1305, selectively diminished under hypoxia
PublicationInduction of proteins involved in drug metabolism and in drug delivery has a significant impact on drug-drug interactions and on the final therapeutic effects. Two antitumor acridine derivatives selected for present studies, C-1748 (9-(2’-hydroxyethylamino)-4-methyl-1-nitroacridine) and C-1305 (5-dimethylaminopropylamino-8-hydroxy-triazoloacridinone), expressed high and low susceptibility to metabolic transformations with liver...
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Progress in targeting tumor cells by using drug-magnetic nanoparticles conjugate.
PublicationTo limit the cytotoxicity of anticancer drugs against healthy cells, an appropriate carrier should be synthesized to deliver the drug to the tumor tissue only. A good solution is to anchor a magnetic nanoparticle to the molecule of the drug and to use a properly directed external magnetic field. We have shown that the improved by us synthesis of the conjugate of doxorubicin with iron-oxide magnetic nanoparticles allows a substantial...
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Synthesis and structure determination of 2,3-diaryl-9,9-dioxo-1H-9-thia-1,4,4a,7,10-pentaazaphenanthrene-2-ols
Publication3-Amino-1,1-dioxopyrido[4,3-e]-1,4,2-dithiazine has been synthesized and applied to the synthesis of 3-amino-2-(4-thioxo-1,4-dihydropyridin-3-ylsulfonyl)guanidine. The reaction of the aminoguanidine with the appropriate 1,2-diarylethane-1,2-diones afforded 2,3-diaryl-9,9-dioxo-1H-9-thia-1,4,4a,7,10-pentaazaphenanthrene-2-ol derivatives. The structure of these compounds, which represent a novel heterocyclic ring system, was confirmed...
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Synthesis of phosphono and phosphate derivatives of hydroxyimino-D-alditols as new potential antifungal agents
PublicationIn search for new effective we antyfungals we focus on two enzymes involved in biosynthesis of the fungal cell wall. The first enzyme is glucosamine-6-phosphate (GlmS), which catalyzes transformation of D-fructose-6-phosphate (Fru-6P) to D-glucosamine-6-phodphate (GlcN-6P) in the chitin biosynthesis pathway. The second enzyme is phosphomannose isomerase (PMI) repored to play a crucial role in biosynthesis of many mannosylated structures,...
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The Effect of Sterols on Amphotericin B Self-Aggregation in a Lipid Bilayer as Revealed by Free Energy Simulations
PublicationAmphotericin B (AmB) is an effective but toxic antifungal drug, known to increase the permeability of the cell membrane, presumably by assembling into transmembrane pores in a sterol-dependent manner. The aggregation of AmB molecules in a phospholipid bilayer is, thus, crucial for the drug’s activity. To provide an insight into the molecular nature of this process, here, we report an atomistic molecular dynamics simulation study...
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Wykorzystanie strategii konia trojańskiego w projektowaniu związków przeciwgrzybowych
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Year 2012
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Absolute configurations of C34 and C35 of antibiotic niphimycin A
PublicationThe relative configurations of four stereogenic centers of the C33-C42 fragment of niphimycin A were assigned as 2S*, 3R*, 4S* and 6S*, based upon 1H NMR analysis with double-quantum filtered COSY and nuclear Overhauser spectroscopy experiments. These data were then correlated with absolute configurations at C36 and C38 of niphimycin A, which were declared previously as 36S and 38S [3]. This allowed for the assignment of the absolute...
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Absolute configurations of C34 and C35 of antibiotic niphimycin A
PublicationThe relative configurations of four stereogenic centers of the C33-C42 fragment of niphimycin A were assigned as 2S*, 3R*, 4S* and 6S*, based upon (1)H NMR analysis with double-quantum filtered COSY and nuclear Overhauser spectroscopy experiments. These data were then correlated with absolute configurations at C36 and C38 of niphimycin A, which were declared previously as 36S and 38S [3]. This allowed for the assignment of the...
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Analityka hormonów płciowych - problemy i wyzwania
PublicationW pracy przedstawiono informacje o przebiegu poszczególnych etapów procedur analitycznych oznaczania związków endokrynnych z grupy hormonów płciowych w próbkach środowiskowych wraz z opisem trudności, które mogą się pojawić przy optymalizacji warunków oznaczania.
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Autofagia: mechanizm molekularny, apoptoza i nowotwory = Autophagy: molecular mechanism, apoptosis and cancer
PublicationW pracy omówiono molekularny mechanizm autofagii oraz najważniejsze szlaki sygnałowe uczestniczące w regulacji przebiegu tego procesu w komórkach nowotworowych. Omówiona została również dwojaka rola autofagii w procesie nowotworzenia oraz skutki zarówno indukcji, jak i inhibicji autofagii w terapii przeciwnowotworowej
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Biofilm Production and Presence of ica and bap Genes in Staphylococcus aureus Strains Isolated from Cows with Mastitis in the Eastern Poland
PublicationThe aim of the study was phenotypic and genotypic analysis of 132 S. aureus strains isolated from mastitis in eastern Poland in respect to their biofilm formation ability. The analysis of the size polymorphism of fragment X in the gene encoding protein A (spa) revealed high genetic differentiation of the analyzed group of isolates. The ability of biofilm formation by the isolates was tested using two phenotypic methods. The Congo...
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Characteristics of hydration water around hen egg lysozyme as the protein model in aqueous solution. FTIR spectroscopy and molecular dynamics simulation
PublicationW niniejszej pracy przedstawiono wyniki badań dotyczące hydratacji białka modelowego - lizozymu z jaja kurzego w roztworze wodnym. Wiodącą techniką stosowaną w badaniach była spektroskopia oscylacyjna FTIR z zastosowaniem techniki rozcieńczenia izotopowego wody półciężkiej HDO w roztworze wody zwykłej. Analiza widma HDO przy pomocy "metody widm zaburzonych" pozwoliła na wyizolowanie widma wody zaburzonej przez lizozym, a tym samym...
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Chemical reactivity and antimicrobial activity of N-substituted maleimides
PublicationZsyntezowano kilkanaście N-podstawionych maleimidów, zawierających w swojej strukturze podstawniki o różnej wielkości i polarności.Maleimidy o charakterze obojętnym wykazywały silny efekt przeciwgrzybowy; ich aktywność przeciwbakteryjna była zróżnicowana. Niską aktywność przeciwbakteryjną, ale wysoką aktywność cytostatyczną stwierdzono dla maleimidów o charakterze zasadowym. Reaktywność chemiczna i lipofilowość miały wpływ na aktywność...
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Coarse-grained simulation - an efficient approach for studying motions of large proteins
PublicationOne of the most important challenges in performing Molecular Dynamics (MD) simulations of large protein complexes is to accommodate the model accuracy and the simulation timescale. Hitherto, for the most relevant dynamics of protein aggregates in an explicit aqueous environment, the timescale reachable for the all-atoms simulations is of hundreds of nanoseconds. This range is four to six orders of magnitude smaller than processes...
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Composition and antimicrobial activity of fatty acids detected in the hygroscopic secretion collected from the secretory setae of larvae of the biting midge Forcipomyia nigra (Diptera: Ceratopogonidae)
PublicationThe hygroscopic secretion produced by the secretory setae of terrestrial larvae of the biting midge Forcipomyia nigra (Winnertz) was analysed using gas chromatography coupled with mass spectrometry (GC-MS). The viscous secretion is stored at the top of each seta and absorbs water from moist air. GC-MS analyses (four independent tests) showed that the secretion contained 12 free fatty acids, the most abundant of which were oleic...
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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
PublicationThe 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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Does the chemical modification of Nystatin A1 affect the drug's ability to overcome the multidrug resistance of fungi?
PublicationAlthough the contemporary medicine keeps moving forward, disseminated infections caused by fungal pathogens are an emerging challenge. The dramatic rise of fungal diseases, especially the most life-threatening systemic mycoses is associated with a permanently growing number of immunodeficient patients. Undoubted difficulties in the treatment of fungal infections are caused by lack of highly effective and selective antifungal drugs,...
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Engineering Candida albicans glucosamine-6-phosphate synthase for efficient enzyme purification
PublicationRationally designed muteins of Candida albicans glucosamine-6-phosphate synthase, an enzyme known as a promising target for antifungal chemotherapy, were constructed, overexpressed in Escherichia coli and purified to near homogeneity. To facilitate and to optimize the purification of the enzyme, three recombinant versionscontaining internal oligoHis fragments were constructed: (i) by substituting residues 343 - 348...
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Genotyping Techniques for Determining the Diversity of Microorganisms
PublicationTyping of microbial pathogens, or identifying bacteria at the strain level, is particularly important for diagnosis, treatment, and epidemiological surveillance of bacterial infections. This is especially the case for bacteria exhibiting high levels of antibiotic resistance or virulence, and those involved in nosocomial or pandemic infections. Strain typing also has applications in studying bacterial population dynamics. The part...
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Imidazoacridinone-dependent lysosomal photodestruction: a pharmacological Trojan horse approach to eradicate multidrug-resistant cancers
PublicationMultidrug 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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Inactivation of glucosamine-6-phosphate synthase by N3-oxoacyl derivatives of L-2,3-diaminopropanoic acid
PublicationN3-oksoacylowe pochodne kwasu l-2,3-diaminopropanowego zawierające ugrupowanie epoksydowe lub układ sprzężonych wiązań podwójnych inaktywują syntaze glukozamino-6-fosforanu (GlcN-6-P) z S. cerevisiae. Wyniki badań kinetycznych inaktywacji enzymu wskazują na dwuetapowy przebieg tej reakcji, przy czym tworzenie kompleksu enzym:ligand poprzedza nieodwracalną modyfikację enzymu. Badane związki różniły się powinowactwem do centrum aktywnego...
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Influence of temperature and interactions with ligands on dissociation of dsDNA and ligand-dsDNA complexes of various types of binding : an electrochemical study.
PublicationSeveral medicinally important compounds that bind to dsDNA strands via intercalation (C-1311, C-1305, EtBr), major groove binding (Hoechst 33258) and covalent binding (cis-Pt) were examined. The obtained results suggest that both the transfer of conformation B to C and the denaturation process, for the ligand-dsDNA complexes, except for covalently bound cis-Pt, took place at higher temperatures compared to the unbound helix. Furthermore,...
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Komórki macierzyste nowotworu i ich znaczenie w diagnostyce i terapii przeciwnowotworowej
PublicationWedług klasycznej teorii karcinogenezy nowotwór powstaje w wyniku ekspansji klonalnej pojedynczej komórki, która uległa transformacji w wyniku nagromadzenia się w jej genomie zmian genetycznych i epigenetycznych. Jednak w ostatnich latach przywołano do życia inną hipotezę, przedstawioną już ponad 150 lat temu, która mówi, że nowotwór wywodzi się ze stransformowanych komórek posiadających cechy komórek pierwotnych (macierzystych)....
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Molecular dynamics and verisimilitude - to what extent can one trust a computational simulation?
PublicationFor the last several tens of years, computer simulations have become of undeniable importance. Molecular Dynamics (MD) simulation techniques are used to examine the phenomena which occur at the level that cannot be observed directly. Thus, they can be successfully exploited in many different scientific fields such as: materials science, applied mathematics and theoretical physics, biochemistry, biophysics or drug design. Despite...
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Novel dendrimeric lipopeptides with antifungal activity
PublicationZaprojektowano, zsyntezowano i scharakteryzowano serię nowych kationowych lipopeptydów zawierających rozgałęziony, amfifilowy polarny rdzeń strukturalny pochodzący od dendronu (Lys)(Lys)(Lys) oraz łańcuchy C8 i C12 na C-końcu. Otrzymane zwiazki wykazywały aktywność przeciwdrobnoustrojową, w tym szczególnie przeciwgrzybową wobec drożdżaków z rodzaju Candida. Najwyższą aktywność, selektywną wobec drobnoustrojów grzybowych, wykazywały...
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PARP inhibition potentiates the cytotoxic activity of C-1305, a selective inhibitor of topoisomerase II, in human BRCA1-positive breast cancer cells
PublicationTwo cellular proteins encoded by the breast and ovarian cancer type 1 susceptibility (BRCA1 and BRCA2) tumor suppressor genes are essential for DNA integrity and the maintenance of genomic stability.Approximately 5-10% of breast and ovarian cancers result from inherited alterations or mutations in these genes.Remarkably, BRCA1/BRCA2-deficient cells are hypersensitive to selective inhibition of poly(ADPribose) polymerase 1 (PARP-1),...