Potentiation of antifungal effect of amphotericin B by squalene, an intermediate for sterol biosynthesis.

Abstract Amphotericin B is a fungicidal substance that is treatment of choice for most systemic fungal infections affecting immunocompromised patients. However, severe side effects have limited the utility of this drug. The aim of this study was to evaluate the antifungal effect of the combination of amphotericin B with black tea or white tea and protective of citotoxic effect. The present study shows that white and black teas have additive effects with amphotericin B against some species Candida. In addition, the combination of white and black tea with amphotericin B may reduce the toxicity of amphotericin B to red blood cells. Our results suggest that white and black tea is a potential agent to combine with amphotericin for antifungal efficacy and to reduce the amphotericin dose to lessen side effects.

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In VitroActivities of a Wide Panel of Antifungal Drugs against Various Scopulariopsis and Microascus Species

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00978-15 ◽

2015 ◽

Vol 59 (9) ◽

pp. 5827-5829 ◽

Cited By ~ 7

Author(s):

Magdalena Skóra ◽

Małgorzata Bulanda ◽

Tomasz Jagielski

Keyword(s):

Amphotericin B ◽

Effective Concentration ◽

Antifungal Drugs ◽

Antifungal Effect ◽

Content Type ◽

Minimal Effective Concentration

ABSTRACTThein vitroactivities of 11 antifungal drugs against 68ScopulariopsisandMicroascusstrains were investigated. Amphotericin B, 5-fluorocytosine, fluconazole, itraconazole, ketoconazole, miconazole, posaconazole, voriconazole, and ciclopirox showed no or poor antifungal effect. The best activities were exhibited by terbinafine and caspofungin, where the MIC and MEC (minimal effective concentration) ranges were 0.0313 to >16 μg/ml and 0.125 to 16 μg/ml, respectively. The MIC and MEC modes were both 1 µg/ml for terbinafine and caspofungin; the MIC50and MEC50were 1 µg/ml for both drugs, whereas the MIC90and MEC90were 4 µg/ml and 16 µg/ml, respectively.

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Eugenol and Isoeugenol In Association with Antifungal Against Cryptococcus neoformans

International Journal of Pharmacognosy and Phytochemical Research ◽

10.25258/phyto.v9i4.8133 ◽

2017 ◽

Vol 9 (4) ◽

Author(s):

Pinheiro L. S. ◽

Sousa J. P. ◽

Barreto N. A. ◽

Dantas T B ◽

...

Keyword(s):

Cryptococcus Neoformans ◽

Amphotericin B ◽

Inhibitory Concentration ◽

Synergistic Effects ◽

Antagonistic Effect ◽

Antifungal Drugs ◽

Antifungal Effect ◽

Beneficial Effects ◽

Combined Use ◽

Antifungal Effects

The antifungal therapy combined is used in clinical practice of several mycoses as it may increase the efficacy of the treatment. The use of natural products (phytochemicals) in combination with conventional antifungal drugs has been related to beneficial effects, mainly synergistic effects. The aim of this study was to evaluate the effect of the combined use of eugenol / isoeugenol, compounds with recognized antimicrobial activity, in association with antifungal amphotericin B against strains of Cryptococcus neoformans. The combined antifungal effect were be determined from the Fraction Inhibitory Concentration index - checkerboard technique. The results obtained in this study showed that eugenol in combination with amphotericin B had antagonistic effect against the strains of C. neoformans, LM 615 and INCQS 40221 (FIC index 6.0 and 4.0), respectively. The combination of the isoeugenol and amphotericin B also showed antagonistic effects for both the LM 615 strain and INCQS 40221 (FIC index 6.0 and 5.0), respectively. This study contributed to the understanding of the antifungal effects of the association of phenylpropanoids (eugenol / isoeugenol) with amphotericin B. Further studies are needed to evaluate and compare the effects of the association of these phytochemicals with other conventional antifungal drugs used against C. neoformans.

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The Antifungal Mechanism of Amphotericin B Elucidated in Ergosterol and Cholesterol-Containing Membranes Using Neutron Reflectometry

Nanomaterials ◽

10.3390/nano10122439 ◽

2020 ◽

Vol 10 (12) ◽

pp. 2439

Author(s):

Robin Delhom ◽

Andrew Nelson ◽

Valerie Laux ◽

Michael Haertlein ◽

Wolfgang Knecht ◽

...

Keyword(s):

Side Effects ◽

Amphotericin B ◽

Antifungal Drug ◽

Neutron Reflectometry ◽

Antifungal Effect ◽

Neutron Reflection ◽

Before And After ◽

Lipid Chain ◽

Molecular Origin ◽

Membrane Thinning

We have characterized and compared the structures of ergosterol- and cholesterol-containing 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) membranes before and after interaction with the amphiphilic antifungal drug amphotericin B (AmB) using neutron reflection. AmB inserts into both pure POPC and sterol-containing membranes in the lipid chain region and does not significantly perturb the structure of pure POPC membranes. By selective per-deuteration of the lipids/sterols, we show that AmB extracts ergosterol but not cholesterol from the bilayers and inserts to a much higher degree in the cholesterol-containing membranes. Ergosterol extraction by AmB is accompanied by membrane thinning. Our results provide new insights into the mechanism and antifungal effect of AmB in these simple models of fungal and mammalian membranes and help understand the molecular origin of its selectivity and toxic side effects.

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