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Search results for: MULTIDRUG RESISTANCE
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Voriconazole and multidrug resistance in Candida albicans
PublicationPorównano aktywność grzybostatyczną in vitro worikonazolu, flukonazolu, ketokonazolu i klotrimazolu wobec opornych na flukonazol szczepów klinicznych Candida albicans oraz rekombinowanych szczepów Saccharomyces cerevisiae eksprymujących jeden z genów kodujących białka oporności wielolekowej (MDR) C. albicans: Cdr1p. Cdr2p lub CaMdr1p. Stwierdzono, że nadekspresja genów MDR czyni komórki drożdżaków mniej wrażliwymi na działanie...
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What about the multidrug resistance in fungi? - comparison of voriconazole and ''old'' azoles.
PublicationPorównano wyniki oznaczeń aktywności przeciwgrzybowej voriconazolu- nowego leku przeciwgrzybowego z pierścieniem azolowym, z lekami poprzedniej generacji. Zaobserwowano znaczny spadek aktywności biologicznej voriconazolu (podobnie jak starszych leków, takich jak fluconazol czy ketoconazol) względem komórek wielolekoopornych, co stanowi przesłankę, że nowy lek jest substratem dla głównych pomp kształtujących zjawisko wielolekooporności...
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The mechanism of overcoming multidrug resistance (MDR) of fungi by amphotericin B and its derivatives
PublicationPrzeprowadzono badania porównawcze w celu określenia aktywności i cytotoksyczności amfoterycyny B (AmB) i jej pochodnych wobec standardowego szczepu S. cerevisiae i jego transformantów zawierających geny C. albicans kodujące białka oporności wielolekowej (MDR) typu ABC i MFS. Pochodne AmB: amid 3-dimetyloaminopropylowy amfoterycyny B oraz ester metylowy N-metylo-N-D-fruktopiranozylo-amfoterycyny B wykazały efekt fungistatyczny...
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MIX2: A Novel Natural Multi-Component Modulator of Multidrug-Resistance and Hallmarks of Cancer Cells
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Strategies for overcoming ABC-transporters-mediated multidrug resistance (MDR) of tumor cells. Review
PublicationOporność wielolekowa (MDR) nowotworów jest główną przyczyną niepowodzeń w chemoterapii przeciwnowotworowej. Jest ona wynikiem nadprodukcji w komórkach opornych transporterów białkowych z nadrodziny ABC, eksportujących cytostatyk z komórki, których działanie uniemożliwia utrzymanie terapeutycznego stężenia leku. W publikacji dokonano przeglądu różnych strategii przeciwdziałania zjawisku MDR. Strategie te dotyczą zarówno kontroli...
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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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The ability to overcome multidrug resistance of tumor cell lines by novel acridine cytostatics with condensed heterocyclic rings
PublicationZbadano aktywność cytotoksyczną, in vitzo dwóch nowych grup cytostatyków akrydynowych zawierających skondensowane pierścienie heterocykliczne w stosunku do komórek nowotworowych linii wrażliwych i opornych. Otrzymane wyniki potwierdziły naszą wcześniejszą hipotezę o istotnej roli pierścieni hetero-cyklicznych w pokonywaniu krzyżowej oporności wielolekowej.
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Search for ABCB1 Modulators Among 2-Amine-5-Arylideneimidazolones as a New Perspective to Overcome Cancer Multidrug Resistance
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Determination of the role of map kinase and PI3K/AKT signaling pathways in the regulation of multidrug resistance proteins in thyroid cancer
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Expression profiles of vault components MVP, TEP1 and vPARP and their correlation to other multidrug resistance proteins in ovarian cancer
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The activity of latent benzoperimidine esters to inhibit P-glycoprotein and multidrug resistance-associated protein 1 dependent efflux of pirarubicin from several lines of multidrug resistant tumor cells.
PublicationZaprezentowano wyniki badań biologicznych przeprowadzonych dla nowej grupy związków: estrów benzoperymidyny z zastosowaniem wybranych linii komórek nowotworowych: wrażliwych i opornych o oporności P-gp-zależnej, MRP1-zależnej i o oporności związanej z nadekspresją białek MRP1/LRP. Metodą spektrofluorymetryczną zbadano zdolność estrów benzoperymidyny do hamowania eksportu aktywnego pirarubicyny z komórek opornych. Estry benzoperymidyny...
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Amphotericin B derivatives: novel strategy for the development of non-toxic, broad spectrum, fungicidal and overcoming multidrug resistance antifungal agents.
PublicationZaprezentowano porównawczą charakterystykę działania amfoterycyny B (AmB) oraz jej pochodnych o różnym stopniu selektywnej toksyczności na szczepy grzybów reperezentujących różne mechanizmy oporności. Były to mutanty C. albicans posiadające defekt w szlaku biosyntezy ergosterolu oraz wielolekooporne szczepy S. cerevisiae wyposażone w pompy eksportujące typu ABC i MFS. Badania obejmowały: 1)porównanie aktywności przeciwgrzybowej...
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The role of structural factors in the kinetics of cellular uptake of pyrazoloacridines and pyrazolopyrimidoakridines. Implications for overcoming multidrug resistance towards leukaemia K562/DOX cells.
PublicationOtrzymano dwie grupy związków: pyrazoloakrydony (PAC) i pyrazolopirymidoakrydony (PPAC). Zbadano molekularne podstawy różnic w aktywności cytotoksycznej otrzymanych związków na poziomie komórkowym wobec komórek opornych linii ludzkiej erytroleukemii K562/DOX z nadekspresją P-glikoproteiny. Zastosowano spektrofluorymetryczną metodę badania transportu związków, która pozwala obserwować zarówno dyfuzję fluoryzujących cząsteczek związku...
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Evaluation of the Role of the Pharmacological Inhibition of Staphylococcus aureus Multidrug Resistance Pumps and the Variable Levels of the Uptake of the Sensitizer in the Strain-Dependent Response of Staphylococcus aureus to PPArg2-Based Photodynamic Ina
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Synthesis and biological evaluation of 2,7-Dihydro-3H-dibenzo[de,h]cinnoli- ne-3,7-done derivatives a novel group of anticancer agents active on a multidrug resistance cell line.
PublicationZsyntezowano serię pochodnych pirydazonu z jednym lub dwoma łańcuchami bocznymi w różnych pozycjach chromoforu tetracyklicznego. Związki wykazały aktywność cytoksyczną na mysią białaczkę L1210 i ludzką k562 oraz na linii komórkowej oporności krzyżowej MDR (k562/DX). Dwa najbardziej aktywne związki przetestowano in vivo na mysiej białaczce P388. Wykazały one aktywność przeciwnowotworową porównywalną z aktywnością Mitoxantronu.
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The role of glucuronidation in drug resistance
PublicationThe final therapeutic effect of a drug candidate, which is directed to a specific molecular target strongly depends on its absorption, distribution, metabolism and excretion (ADME). The disruption of at least one element of ADME may result in serious drug resistance. In this work we described the role of one element of this resistance: phase II metabolism with UDP-glucuronosyltransferases (UGTs). UGT function is the transformation...
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Chemosensitization of multidrug resistant Candida albicans by the oxathiolone fused chalcone derivatives
PublicationThree structurally related oxathiolone fused chalcone derivatives appeared effective chemosensitizers, able to restore in part sensitivity to fluconazole of multidrug-resistant C.albicans strains. Compound 21 effectively chemosensitized cells resistant due to the overexpression of the MDR1 gene, compound 6 reduced resistance of cells overexpressing the ABC-type drug transporters CDR1/CDR2 and derivative 18 partially reversed fluconazole...
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Voriconazole-Based Salts Are Active against Multidrug-Resistant Human Pathogenic Yeasts
PublicationVoriconazole (VOR) hydrochloride is unequivocally converted into VOR lactates and valinates upon reaction with silver salts of organic acids. This study found that the anticandidal in vitro activity of these compounds was comparable or slightly better than that of VOR. The Candida albicans clinical isolate overexpressing CaCDR1/CaCDR2 genes, highly resistant to VOR, was apparently more susceptible to VOR salts. On the other hand,...
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Antimicrobial resistance of Pseudomonas spp. isolated from wastewater and wastewater-impacted marine coastal zone
PublicationIn this study, species distribution and antimicrobial susceptibility of cultivated Pseudomonas spp. were studied in influent (INF), effluent (EFF), and marine outfall (MOut) of wastewater treatment plant (WWTP). The susceptibility was tested against 8 antimicrobial classes, active against Pseudomonas spp.: aminoglycosides, carbapenems, broad-spectrum cephalosporins from the 3rd and 4th generation, extended-spectrum penicillins,...
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Correlation between the number of Pro-Ala repeats in the EmrA homologue of Acinetobacter baumannii and resistance to netilmicin, tobramycin, imipenem and ceftazidime
PublicationAcinetobacter baumannii coccobacilli are dangerous to patients in intensive care units because of their multidrug resistance to antibiotics, developed mainly in the past decade. This study aimed to examine whether there is a significant correlation between the number of Pro-Ala repeats in the CAP01997 protein, the EmrA homologue of A. baumannii, and resistance to antibiotics. A total of 79 multidrug-resistant A. baumannii strains...
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Urinary Tract Infections Caused by K. pneumoniae in Kidney Transplant Recipients – Epidemiology, Virulence and Antibiotic Resistance
PublicationUrinary tract infections are the most common complication in kidney transplant recipients, possibly resulting in the deterioration of a long-term kidney allograft function and an increased risk of recipient’s death. K. pneumoniae has emerged as one of the most prevalent etiologic agents in the context of recurrent urinary tract infections, especially with multidrug resistant strains. This paper discusses the epidemiology and risk...
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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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Comparative Assessment of Bacteriophage and Antibiotic Activity against Multidrug-Resistant Staphylococcus aureus Biofilms
PublicationProblems connected with biofilm-related infections and antibiotic resistance necessitate the investigation and development of novel treatment strategies. Given their unique characteristics, one of the most promising alternatives to conventional antibiotics are bacteriophages. In the in vitro and in vivo larva model study, we demonstrate that phages vB_SauM-A, vB_SauM-C, and vB_SauM-D are effective antibiofilm agents. The exposure...
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Antibiotic resistance and prevalence of class 1 and 2 integrons in Escherichia coli isolated from two wastewater treatment plants, and their receiving waters (Gulf of Gdansk, Baltic Sea, Poland)
PublicationIn this study, antimicrobial-resistance patterns were analyzed in Escherichia coli isolates from raw (RW) and treated wastewater (TW) of two wastewater treatment plants (WWTPs), their marine outfalls (MOut), and mouth of the Vistula River (VR). Susceptibility of E. coli was tested against different classes of antibiotics. Isolates resistant to at least one antimicrobial agent were PCR tested for the presence of integrons. Ampicillin-resistant...
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Targeting yeast topoisomerase II by imidazo and triazoloacridinone derivatives resulting in their antifungal activity
PublicationFungal pathogens are considered as serious factors for deadly diseases and are a case of medical concern. Invasive fungal infections also complicate the clinical course of COVID-19, leading to a significant increase in mortality. Furthermore, fungal strains' multidrug resistance has increased the demand for antifungals with a different mechanism of action. The present study aimed to identify antifungal compounds targeting yeast...
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Antibiotic Resistance of Uropathogens Isolated from Patients Hospitalized in District Hospital in Central Poland in 2020
PublicationThe aim of this study was to determine antibiotic resistance patterns and the prevalence of uropathogenes causing urinary tract infections (UTIs) in patients hospitalized in January–June 2020 in central Poland. Antimicrobial susceptibility testing was performed using the disk-diffusion method. Escherichia coli (52.2%), Klebsiella pneumoniae (13.7%), Enterococcus faecalis (9.3%), E. faecium (6.2%), and Proteus mirabilis (4,3%) were...
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Drug-resistant and hospital-associated Enterococcus faecium from wastewater, riverine estuary and anthropogenically impacted marine catchment basin.
PublicationEnterococci, ubiquitous colonizers of humans and other animals, play an increasingly important role in health-care associated infections (HAIs). Acquisition of resistance determinants not only seriously limits available therapeutic options but also increases available gene pool for other species. It is believed that the recent evolution of two clinically relevant species, Enterococcus faecalis and Enterococcus faecium occurred...
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Discrimination of hospital isolates of Acinetobacter baumannii using repeated sequences and whole genome alignment differential analysis
PublicationAn optimized method for bacterial strain differentiation, based on combination of Repeated Sequences and Whole Genome Alignment Differential Analysis (RS&WGADA), is presented in this report. In this analysis, 51 Acinetobacter baumannii multidrug-resistance strains from one hospital environment and patients from 14 hospital wards were classified on the basis of polymorphisms of repeated sequences located in CRISPR region, variation...
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Antifungal dipeptides incorporating an inhibitor of homoserine dehydrogenase
PublicationThe antifungal activity of 5‐hydroxy‐4‐oxo‐L‐norvaline (HONV), exhibited under conditions mimicking human serum, may be improved upon incorporation of this amino acid into a dipeptide structure. Several HONV‐containing dipeptides inhibited growth of human pathogenic yeasts of the Candida genus in the RPMI‐1640 medium, with minimal inhibitory concentration values in the 32 to 64 μg mL−1 range. This activity was not affected by multidrug...
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Emerging anticancer activity of candidal glucoseamine-6-phosphate synthase inhibitors upon nanoparticle-mediated delivery
PublicationNumerous glutamine analogues have been reported as irreversible inhibitors of the glucosamine-6-phosphate (GlcN-6-P) synthase in pathogenic Candida albicans in the last 3.5 decades. Among the reported inhibitors, the most effective N3-(4-methoxyfumaroyl)-L-2,3- diaminopropanoic acid (FMDP) has been extensively studied in order to develop its more active analogues. Several peptide−FMDP conjugates were tested to deliver FMDP to its...
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Targeting DNA Topoisomerase II in Antifungal Chemotherapy.
PublicationTopoisomerase inhibitors have been in use clinically for the treatment of several diseases for decades. Although those enzymes are significant molecular targets in antibacterial and anticancer chemotherapy very little is known about the possibilities to target fungal topoisomerase II (topo II). Raising concern for the fungal infections, lack of effective drugs and a phenomenon of multidrug resistance underlie a strong need to expand...
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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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‘Acridines’ as New Horizons in Antifungal Treatment
PublicationFrequent fungal infections in immunocompromised patients and mortality due to invasive mycosis are important clinical problems. Opportunistic pathogenic Candida species remain one of the leading causes of systemic mycosis worldwide. The repertoire of antifungal chemotherapeutic agents is very limited. Although new antifungal drugs such as lanosterol 14α-demethylase and β-glucan synthase inhibitors have been introduced into clinical...
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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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Drug-drug interaction potential of antitumor acridine agent C-1748: The substrate of UDP-glucuronosyltransferases 2B7, 2B17 and the inhibitor of 1A9 and 2B7
PublicationBackground The compound 9-(2′-hydroxyethylamino)-4-methyl-1-nitroacridine (C-1748), the promising antitumor agent developed in our laboratory was determined to undergo phase I metabolic pathways. The present studies aimed to know its biotransformation with phase II enzymes – UDP-glucuronosyltransferases (UGTs) and its potential to be engaged in drug-drug interactions arising from the modulation of UGT activity. Methods UGT-mediated...
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Biofilm Formation and Prevalence of Biofilm-Related Genes Among Clinical Strains of Multidrug-Resistant Staphylococcus aureus
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Structural and dynamic changes adopted by EmrE, multidrug transporter protein—Studies by molecular dynamics simulation
PublicationEmrE protein transports positively charged aromatic drugs (xenobiotics) in exchange for two protons and thus provides bacteria resistance to variety of drugs. In order to understand how this protein may recognize ligands, the monomer and asymmetric apo-form of the EmrE dimer embedded in a heterogeneous phospholipid (POPE + POPG) membrane were studied by molecular dynamics simulations. Dimer is regarded as a functional form of the...
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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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A Novel Cryptic Clostridial Peptide That Kills Bacteria by a Cell Membrane Permeabilization Mechanism
PublicationThis work reports detailed characteristics of the antimicrobial peptide Intestinalin (P30), which is derived from the LysC enzyme of Clostridium intestinale strain URNW. The peptide shows a broader antibacterial spectrum than the parental enzyme, showing potent antimicrobial activity against clinical strains of Gram-positive staphylococci and Gram-negative pathogens and causing between 3.04 ± 0.12 log kill for Pseudomonas aeruginosa...
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Imidazoacridinone antitumor agent C-1311 as a selective mechanism- based inactivator of human cytochrome P450 1A2 and 3A4 isoenzymes.
Publication5-Diethylaminoethylamino-8-hydroxyimidazoacridinone (C-1311), a promising antitumor agent that is also active against autoimmune diseases, was determined to be a selective inhibitor of the cytochrome P450 (CYP) 1A2 and 3A4 isoenzymes. Therefore, C-1311 might modulate the effectiveness of other drugs used in multidrug therapy. The present work aimed to identify the mechanism of the observed C-1311-mediated inactivation of CYP1A2...