Amphotericin B–copper(II) complex as a potential agent with higher antifungal activity against Candida albicans

Chudzik, Barbara; Tracz, Izabela B.; Czernel, Grzegorz; Fiołka, Marta J.; Borsuk, Grzegorz; Gagoś, Mariusz

doi:10.1016/j.ejps.2013.06.007

Cited by 39 publications

(26 citation statements)

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“…Previous studies showed that such modifications improved fungicidal activity of AmB (Chudzik et al, 2013). The question was how such complexes can influence human cells.…”

Section: Discussionmentioning

confidence: 99%

“…One of the methods is to form a complex of AmB with copper(II) ions. Such an AmB-Cu 2+ complex was shown to be stable at physiological pH and to retain high bioactivity (Gagoś et al, 2011;Chudzik et al, 2013). The reasons for using the copper ions are their fungicidal and bactericidal properties (Spampinato and Leonardi, 2013).…”

Section: Introductionmentioning

confidence: 99%

“…The reasons for using the copper ions are their fungicidal and bactericidal properties (Spampinato and Leonardi, 2013). These properties are related to the ability of the element to transport electrons, resulting in the formation of free radicals (Chudzik et al, 2013). A hypothesis suggests that the presence of copper ions in the molecule of AmB can increase its antifungal activity in lower concentrations (Chudzik et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

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Expression profiles of genes related to melatonin and oxidative stress in human renal proximal tubule cells treated with antibiotic amphotericin B and its modified forms

Gola

Skubis²,

Sikora³

et al. 2015

Turk J Biol

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It acts through membrane receptors (MT1 and MT2), nuclear receptors (ROR/RZR -retinoid orphan receptors/ retinoid Z receptors), and nonreceptor-mediated mechanisms (Slominski et al., 2012). Melatonin, through its antioxidant properties, protects against damage of cellular components including DNA, cytosolic proteins, and cell membrane lipids (Yürüker et al., 2015). Studies on the antioxidant properties of melatonin are most commonly associated with agents that induce free radicals in cells (Nazıroğlu et al., 2013). Antibiotics also induce the generation of free radicals. One of them, amphotericin B (AmB), causes lipid peroxidation through generation of reactive oxygen species (ROS). AmB belongs to the group of polyene antibiotics and is an effective antifungal drug commonly used to treat systemic mycoses. It is believed that the fungicidal activity is due to the binding of AmB with the ergosterol present in the cell membrane of fungi, resulting in membrane permeabilization and osmotic imbalance (Brajtburg et al., 1990;Paulo et al., 2013). One of the mechanisms leading to fungal cell death is leakage of potassium ions caused by formation of ion channels in the cell membrane as a consequence of AmB binding with ergosterol (Chudzik et al., 2015). This situation leads to the generation of ROS and lipid peroxidation (Mesa-Arango et al., 2012). Unfortunately, AmB, besides its affinity to ergosterol, also shows an affinity to cholesterol present in human cell membranes, causing nephrotoxic and hepatotoxic side effects (Antonowicz-Juchniewicz et al.

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“…Previous studies showed that such modifications improved fungicidal activity of AmB (Chudzik et al, 2013). The question was how such complexes can influence human cells.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Expression profiles of genes related to melatonin and oxidative stress in human renal proximal tubule cells treated with antibiotic amphotericin B and its modified forms

Gola

Skubis²,

Sikora³

et al. 2015

Turk J Biol

Self Cite

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“…The principal and commonly accepted mechanism of action of this antibiotic is based on the formation of an oligomeric pore structure within the fungal plasma membrane (PM) by interaction with membrane sterols. This leads to the flux of cations, cell membrane depolarization and cell death [1][2][3]. Unfortunately, owing to operation of very similar mechanisms in human cells, AmB is also highly toxic to patients.…”

Section: Introductionmentioning

confidence: 99%

ABCA1 transporter reduces amphotericin B cytotoxicity in mammalian cells

Grela

Wójtowicz

et al. 2019

Cell. Mol. Life Sci.

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Amphotericin B (AmB) belongs to a group of polyene antibiotics commonly used in the treatment of systemic mycotic infections. A widely accepted mechanism of action of AmB is based on the formation of an oligomeric pore structure within the plasma membrane (PM) by interaction with membrane sterols. Although AmB binds preferentially to ergosterol, it can also bind to cholesterol in the mammalian PM and cause severe cellular toxicity. The lipid content and its lateral organization at the cell PM appear to be significant for AmB binding. Several ATP-binding cassette (ABC) transporters, including ABCA1, play a crucial role in lipid translocation, cholesterol redistribution and efflux. Here, we demonstrate that cells expressing ABCA1 are more resistant to AmB treatment, while cells lacking ABCA1 expression or expressing non-active ABCA1MM mutant display increased sensitivity. Further, a FLIM analysis of AmB-treated cells reveals a fraction of the antibiotic molecules, characterized by relatively high fluorescence lifetimes (> 6 ns), involved in formation of bulk cholesterol-AmB structures at the surface of ABCA1-expressing cells. Finally, lowering the cellular cholesterol content abolishes resistance of ABCA1-expressing cells to AmB. Therefore, we propose that ABCA1-mediated cholesterol efflux from cells induces formation of bulk cholesterol-AmB structures at the cell surface, preventing AmB cytotoxicity. Keywords Plasma membrane • Raw 264.7 macrophages • CHO-K1 • MTT cytotoxicity assays • FLIM • Fluorescence anisotropy Abbreviations A1G ABCA1-GFP ABC ATP-binding cassette transporter AmB Amphotericin B ApoAI Apolipoprotein AI CHO-K1 Chinese hamster ovary K1 cells eGFP Enhanced green fluorescent protein FACS Fluorescence-activated cell sorting or flow cytometry FLIM Fluorescence lifetime imaging microscopy HDL High-density lipoprotein LXR Liver X receptor MMG ABCA1MM-GFP MTT 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide MβCD Methyl-β-cyclodextrin NMR Nuclear magnetic resonance PGK Phosphoglycerate kinase PM Plasma membrane RCT Reverse cholesterol pathway ZA Zaragozic acid ΔFBS Delipidated FBS Cellular and Molecular Life Sciences

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“…0.5 ml of vesicular gel solution (1 μg of drug) is placed into one bore which is noted with '1' and 0.5 ml of marketing gel solution (1 μg of drug) is kept in the bore cup which is named with '4' similarly the third '2' and fourth '3' bore for other two formulations. The petri dish was maintained at room temperature for 1 h and incubated at 37°C for 24 h. The zones of minimum inhibition were recorded in every pore [18,20,21].…”

Section: Antifungal Activity Of Optimized Formulationsmentioning

confidence: 99%

Optimization and Evaluation of Oleic Acid Based Unsaturated Fatty Acid Liposomes Gel

Kaur¹,

Garg²

2017

J Bioequiv Availab

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Amphotericin B–copper(II) complex as a potential agent with higher antifungal activity against Candida albicans

Cited by 39 publications

References 50 publications

Expression profiles of genes related to melatonin and oxidative stress in human renal proximal tubule cells treated with antibiotic amphotericin B and its modified forms

Expression profiles of genes related to melatonin and oxidative stress in human renal proximal tubule cells treated with antibiotic amphotericin B and its modified forms

ABCA1 transporter reduces amphotericin B cytotoxicity in mammalian cells

Optimization and Evaluation of Oleic Acid Based Unsaturated Fatty Acid Liposomes Gel

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