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József Molnár

Bio: József Molnár is an academic researcher from University of Szeged. The author has contributed to research in topics: Multiple drug resistance & Efflux. The author has an hindex of 21, co-authored 68 publications receiving 1363 citations. Previous affiliations of József Molnár include Albert Szent-Györgyi Medical University & Centre national de la recherche scientifique.


Papers
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Journal ArticleDOI
TL;DR: The role of quorum sensing is well known in microbial pathogenicity and antibiotic resistance, and the inhibition of QS signals reduces the problem of resistance and virulence.
Abstract: The role of quorum sensing (QS) is well known in microbial pathogenicity and antibiotic resistance. QS is responsible for motility, swarming, and biofilm production based on the signal molecules, e.g., acylated homoserine lactones (AHLs) produced by micro-organisms above certain population density. The inhibition of QS may reduce pathogenicity, antibiotic resistance and biofilm formation in systemic and local infections. The homoserine lactones and other transmitters contribute to antibiotic resistance and pathogenicity of several bacteria; consequently the inhibition of QS signals reduces the problem of resistance and virulence. Due to the increasing number of persistent non-treatable infections, there is an urgent need to develop new strategies to combat infections that destabilize bacterial communities in the host. The effect of essential oils on bacterial growth and QS were evaluated using the sensor strain Chromobacterium violaceum CV026 and N-acyl homoserine lactone (AHL) producing Escherichia coli ATTC 31298 and the grapevine colonizing Ezf 10-17 strains. Of the tested oils, rose, geranium, lavender and rosemary oils were the most potent QS inhibitors. Eucalyptus and citrus oils moderately reduced pigment production by CV026, whereas the chamomile, orange and juniper oils were ineffective.

139 citations

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TL;DR: Three alkaloids, lycorine, homolycorine and 2- O-acetylly Corine, were isolated from the bulbs of Leucojum vernum (Amaryllidaceae) and identified by means of NMR analysis and demonstrate that trisphaeridine, lyCorine, Homolycorines and haemanthamine possess high antiretroviral activities.
Abstract: Three alkaloids, lycorine, homolycorine and 2- O-acetyllycorine, were isolated from the bulbs of Leucojum vernum (Amaryllidaceae) and identified by means of NMR analysis The alkaloids obtained from L vernum and from other Amaryllidaceae species were studied in vitro for HIV-1 replication inhibitory activity on MT4 cells The cytotoxicity of the compounds in uninfected cells was evaluated by using the MTT assay and the [ (3)H]thymidine incorporation test The antiviral activities were determined by means of the p24 antigen assay and solid-phase reverse transcriptase testing The results demonstrate that trisphaeridine, lycorine, homolycorine, and haemanthamine possess high antiretroviral activities (IC (50) = 04 - 73 microg/mL), accompanied by low therapeutic indices (TI (50) = 13 - 19)

137 citations

Journal Article
TL;DR: This report demonstrates the development of rational models for drug resistance MCF-7 cell lines and reversal of acquired drug resistance.
Abstract: Backgroud: The effectiveness of chemotherapy is limited by the emergence of multidrug resistance (MDR). MDR is caused by the activity of various ATP binding cassette (ABC) transporters that pump anticancer drugs out of the cells in an ATP-dependent manner. Additionally some other cellular mechanisms of MDR have been reported. The purpose of this study was to investigate mechanisms of MDR in drug resistant MCF-7 cell lines and to modulate P-glycoprotein (P-gp) and MRP1-based MDR. Materials and Methods: Paclitaxel (MCF- 7/Pac), docetaxel (MCF-7/Doc), doxorubicin (MCF-7/Dox) and vincristine (MCF-7/Vinc) resistant sublines were developed from the parent MCF-7 cell line (MCF-7/S) by stepwise selection in dose increments over two years. Flow cytometry, MTT cytotoxicity assay, RT-PCR, caspase-3 activity assay and checkerboard combination assay were performed to investigate the degree of resistance developed in sublines and to reverse drug resistance phenotype. Results: The flow cytometry histograms of drug accumulation assays demonstrated that the drug-resistant cell lines are P-gp and MRP1 positive. RT-PCR results showed that the resistant sublines express both MDR1 and MRP1 genes. Resistance indices of each subline to each anticancer drug were determined using the MTT cytotoxicity assay and it was found that all the sublines were resistant to their respective agents. Caspase-3 activities of the cell lines were also determined. Caspase-3 activity is an important indicator of apoptosis in the cell. The reversal of MDR was attempted by two cinnamylidene ketone and two organosilicon compounds. The results indicated that these compounds modulated P-gp effectively, but they were not very effective at reversing MRP1 activity in the MCF-7 sublines. Four selective anticancer drugs (paclitaxel, docetaxel, doxorubicin and vincristine) and four

109 citations

Journal ArticleDOI
TL;DR: The results suggest that pharmacokinetic studies should be performed prior to concomitant clinical use of such drugs which block P-glycoprotein function, which occurs in resistant cancer cells, in human intestine and in the blood-brain barrier.

56 citations

Journal ArticleDOI
TL;DR: The dried aerial parts of Euphorbia mongolica afforded three new acylated polyhydroxy diterpenoids based on the jatrophane framework that demonstrated a concentration-dependent effect in inhibiting the efflux pump activity of these tumor cells.
Abstract: The dried aerial parts of Euphorbia mongolica afforded three new acylated polyhydroxy diterpenoids based on the jatrophane framework. The structures were established by means of a combination of 1D and 2D NMR techniques and mass spectrometry as (2S*,3S*,4R*,5R*,7S*,8R*,13S*,15R*)-5α,7β,8α-triacetoxy-3β-benzoyloxy-15β-hydroxyjatropha-6(17),11E-diene-9,14-dione (1), (2S*,3S*,4R*,5R*,7S*,8S*,9S*13S*,15R*)-5α,7β,8α,9α,15β-pentaacetoxy-3β-benzoyloxyjatropha-6(17),11E-dien-14-one (2), and (2S*,3S*,4R*,5R*,7S*,8S*,9S*13S*,15R*)-3β,7β,8α,9α,15β-pentaacetoxy-5α-benzoyloxyjatropha-6(17),11E-dien-14-one (3). When the isolates were assayed for multidrug resistance-reversing activity in a rhodamine 123 exclusion test using L5178 mouse lymphoma cells, all compounds demonstrated a concentration-dependent effect in inhibiting the efflux pump activity of these tumor cells in the range 11.2−112 μM.

56 citations


Cited by
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TL;DR: In this Review, the fundamental characteristics of azide chemistry and current developments are presented and the focus will be placed on cycloadditions (Huisgen reaction), aza ylide chemistry, and the synthesis of heterocycles.
Abstract: Since the discovery of organic azides by Peter Griess more than 140 years ago, numerous syntheses of these energy-rich molecules have been developed. In more recent times in particular, completely new perspectives have been developed for their use in peptide chemistry, combinatorial chemistry, and heterocyclic synthesis. Organic azides have assumed an important position at the interface between chemistry, biology, medicine, and materials science. In this Review, the fundamental characteristics of azide chemistry and current developments are presented. The focus will be placed on cycloadditions (Huisgen reaction), aza ylide chemistry, and the synthesis of heterocycles. Further reactions such as the aza-Wittig reaction, the Sundberg rearrangement, the Staudinger ligation, the Boyer and Boyer-Aube rearrangements, the Curtius rearrangement, the Schmidt rearrangement, and the Hemetsberger rearrangement bear witness to the versatility of modern azide chemistry.

1,766 citations

Journal ArticleDOI
TL;DR: An overview of Pd-catalyzed N-arylation reactions found in both basic and applied chemical research from 2008 to the present is provided.
Abstract: Pd-catalyzed cross-coupling reactions that form C–N bonds have become useful methods to synthesize anilines and aniline derivatives, an important class of compounds throughout chemical research. A key factor in the widespread adoption of these methods has been the continued development of reliable and versatile catalysts that function under operationally simple, user-friendly conditions. This review provides an overview of Pd-catalyzed N-arylation reactions found in both basic and applied chemical research from 2008 to the present. Selected examples of C–N cross-coupling reactions between nine classes of nitrogen-based coupling partners and (pseudo)aryl halides are described for the synthesis of heterocycles, medicinally relevant compounds, natural products, organic materials, and catalysts.

1,709 citations

Journal Article
TL;DR: In this paper, the U.S. Public Health Service (USPS) recommended HIV post-exposure prophylaxis (PEP) regimens have been changed.
Abstract: Summary This report updates U.S. Public Health Service recommendations for the management of health-care personnel (HCP) who have occupational exposure to blood and other body fluids that might contain human immunodeficiency virus (HIV). Although the principles of exposure management remain unchanged, recommended HIV postexposure prophylaxis (PEP) regimens have been changed. This report emphasizes adherence to HIV PEP when it is indicated for an exposure, expert consultation in management of exposures, follow-up of exposed workers to improve adherence to PEP, and monitoring for adverse events, including seroconversion. To ensure timely postexposure management and administration of HIV PEP, clinicians should consider occupational exposures as urgent medical concerns.

1,310 citations

Journal ArticleDOI
TL;DR: The increasing resistance of microorganisms to conventional chemicals and drugs is a serious and evident worldwide problem that has prompted research into the identification of new biocides with broad activity.
Abstract: The increasing resistance of microorganisms to conventional chemicals and drugs is a serious and evident worldwide problem that has prompted research into the identification of new biocides with broad activity. Plants and their derivatives, such as essential oils, are often used in folk medicine. In nature, essential oils play an important role in the protection of plants. Essential oils contain a wide variety of secondary metabolites that are capable of inhibiting or slowing the growth of bacteria, yeasts and moulds. Essential oils and their components have activity against a variety of targets, particularly the membrane and cytoplasm, and in some cases, they completely change the morphology of the cells. This brief review describes the activity of essential oils against pathogenic bacteria.

1,281 citations

Journal ArticleDOI
01 Jan 2004-Drugs
TL;DR: Fluoroquinolones and β-lactams of the latest generations are likely to select for overproduction mutants of these pumps and make the bacteria resistant in one step to practically all classes of antibacterial agents.
Abstract: Drug efflux pumps play a key role in drug resistance and also serve other functions in bacteria. There has been a growing list of multidrug and drug-specific efflux pumps characterized from bacteria of human, animal, plant and environmental origins. These pumps are mostly encoded on the chromosome, although they can also be plasmid-encoded. A previous article in this journal provided a comprehensive review regarding efflux-mediated drug resistance in bacteria. In the past 5 years, significant progress has been achieved in further understanding of drug resistance-related efflux transporters and this review focuses on the latest studies in this field since 2003. This has been demonstrated in multiple aspects that include but are not limited to: further molecular and biochemical characterization of the known drug efflux pumps and identification of novel drug efflux pumps; structural elucidation of the transport mechanisms of drug transporters; regulatory mechanisms of drug efflux pumps; determining the role of the drug efflux pumps in other functions such as stress responses, virulence and cell communication; and development of efflux pump inhibitors. Overall, the multifaceted implications of drug efflux transporters warrant novel strategies to combat multidrug resistance in bacteria.

1,118 citations