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Home / Archives for Spengler G

Possible Biological and Clinical Applications of Phenothiazines

  • Authors: Amaral L, Csonka Á, Molnar J, Spengler G, Varga B
  • Publication Year: 2017
  • Journal: Anticancer Research
  • Link: https://www.ncbi.nlm.nih.gov/pubmed/29061777

Phenothiazines have been used in many areas of medicine, mainly in psychopharmacology. These compounds are able to effectively inhibit dopamine, histamine, serotonin, acetylcholine, and α-adrenergic receptors; thus, their effect and side-effect profiles are extremely diverse. Besides their antipsychotic activity, phenothiazines have a significant antimicrobial effect as well, since they can enhance the bactericidal function of macrophages and inhibit efflux pumps. They are also able to eliminate bacterial resistance plasmids and destroy bacteria by their membrane-destabilizing effect. Their antiviral, antiprotozoal, antifungal, and antiprion activities have also been described. Phenothiazines have also been proven to destroy cancer cells and sensitize them to chemotherapy. Anti-angiogenesis and anticancer stem cell activities have also been reported, and they might be applied as adjuvants in the treatment of infections and tumors in the future. Finally, phenothiazines can also be effective in the treatment of neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease.
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New Roads Leading to Old Destinations: Efflux Pumps as Targets to Reverse Multidrug Resistance in Bacteria

  • Authors: Amaral L, Gajdács M, Kincses A, Spengler G
  • Publication Year: 2017
  • Journal: Molecules
  • Link: https://www.ncbi.nlm.nih.gov/pubmed/28294992

Multidrug resistance (MDR) has appeared in response to selective pressures resulting from the incorrect use of antibiotics and other antimicrobials. This inappropriate application and mismanagement of antibiotics have led to serious problems in the therapy of infectious diseases. Bacteria can develop resistance by various mechanisms and one of the most important factors resulting in MDR […]
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Fluorimetric methods for analysis of permeability, drug transport kinetics, and inhibition of the ABCB1 membrane transporter

  • Authors: Amaral L, Armada A, Martins C, Molnar J, Rodrigues AS, Spengler G, Viveiros M
  • Publication Year: 2016
  • Journal: Cancer Drug Resistance
  • Link: https://link.springer.com/protocol/10.1007%2F978-1-4939-3347-1_7%20

The cell membrane P-glycoprotein (P-gp; MDR1, ABCB1) is an energy-dependent efflux pump that belongs to the ATP-binding cassette (ABC) family of transporters, and has been associated with drug resistance in eukaryotic cells. Multidrug resistance (MDR) is related to an increased expression and function of the ABCB1 (P-gp) efflux pump that often causes chemotherapeutic failure in […]
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Role of calcium in the efflux system of Escherichia coli.

  • Authors: Amaral L, Cerca P, Costa S, Machado L, Martins A, Spengler G, Viveiros M
  • Journal: International Journal of Antimicrobial Agents
  • Link: http://www.ncbi.nlm.nih.gov/pubmed/?term=Role+of+calcium+in+the+efflux+system+of+Escherichia+coli.

Efflux of antibiotics by Escherichia coli AG100 is performed by a variety of efflux pumps, ensuring survival of the bacterium in widely diverse media. At pH 5, efflux is independent of metabolic energy during the period of time the assay is conducted; at pH 8 it is totally dependent upon metabolic energy.
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Genetic response of Salmonella enterica serotype Enteritidis to thioridazine rendering the organism resistant to the agent.

  • Authors: Amaral L, Cerca P, Costa SS, Couto I, Fanning S, Machado L, Martins A, Martins M, McCusker M, Molnar J, Ntokou E, Rodrigues L, Spengler G, Viveiros M
  • Journal: International Journal of Antimicrobial Agents
  • Link: http://www.ncbi.nlm.nih.gov/pubmed/?term=Genetic+response+of+Salmonella+enterica+serotype+Enteritidis+to+thioridazine+rendering+the+organism+resistant+to+the+agent

Thioridazine (TZ)-induced accumulation of the universal efflux pump substrate ethidium bromide and its subsequent efflux by Salmonella strains with various degrees of overexpressed efflux pumps takes place automatically at pH 7.4, is independent of a metabolic source, is not affected by a proton ionophore and is precluded by palmitic acid.
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GHTM is a R&D Unit that brings together researchers with a track record in Tropical Medicine and International & Global Health. It aims at strengthening Portugal's role as a leading partner in the development and implementation of a global health research agenda. Our evidence-based interventions contribute to the promotion of equity in health and to improve the health of populations.

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