In vitro activities of antifungal agents alone and in combination against fluconazole-susceptible and -resistant strains of Candida dubliniensis

Scheid, Liliane Alves; Mario, Débora Alves Nunes; Kubiça, Thaís Felli; Santurio, Jânio M.; Alves, Sydney Hartz

doi:10.1590/s1413-86702012000100014

Cited by 2 publications

(3 citation statements)

References 12 publications

(21 reference statements)

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“…The resulting ergosterol depletion and squalene accumulation affects membrane structure and function (Campoy and Adrio, 2017). We suppose that these changes in the lipid composition of C. glabrata membranes may enhance the killing effectivity of styrylpyridinium compounds, since some reports have already described an increased efficiency of terbinafine in combination with other antifungal drugs on C. albicans or C. dubliniensis (Barchiesi et al, 1998;Scheid et al, 2012).…”

Section: Synergistic Effect Of Styrylpyridinium Compounds With Antifumentioning

confidence: 99%

Styrylpyridinium Derivatives as New Potent Antifungal Drugs and Fluorescence Probes

et al. 2020

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The incidence of Candida glabrata infections increases every year due to its higher resistance to commonly used antifungal drugs. We characterized the antifungal mechanism of action of eight new styrylpyridinium derivatives, with various N-alkyl chains (-C 6 H 13 ,-C 8 H 17 ,-C 10 H 21 ,-C 12 H 25) and different substituents, on C. glabrata strains differing in their drug resistance due to the presence or absence of two major drug-efflux pumps. We found that the tested styrylpyridinium compounds affected the growth of C. glabrata cells in a compound-and strain-dependent manner, and apparently they were substrates of CgCdr1 and CgCdr2 pumps. Further, we determined the impact of the tested compounds on plasma membrane integrity. The ability to cause damage to a plasma membrane depended on the compound, its concentration and the presence of efflux pumps, and corresponded well with the results of growth and survival tests. We also tested possible synergism with three types of known antifungal drugs. Though we did not observe any synergism with azole drugs, styrylpyridinium compounds 5 and 6 together with FK506 demonstrated excellent antifungal properties, whereas compounds 2, 3, 5, and 6 exhibited a significant synergistic effect in combination with terbinafine. Based on our results, derivatives 2 and 6 turned out to be the most promising antifungal drugs. Moreover, compound 6 was not only able to effectively permeabilize the yeast plasma membrane, but also exhibited significant synergism with FK506 and terbinafine. Finally, we also characterized the spectroscopic properties of the tested styrylpyridinium compounds. We measured their absorption and fluorescence spectra, determined their localization in yeast cells and found that their fluorescence characteristics differ from the properties of current commercial vacuolar styrylpyridinium markers and allow multi-color staining. Compounds 1, 3, 7, and 8 were able to accumulate in plasma and vacuolar membranes, and compounds 2, 5, and 6 stained the whole interior of dead cells. In summary, of the eight tested compounds, compound 6 is the most promising antifungal drug, compound 8, due to its minimal toxicity, is the best candidate for a new vacuolar-membrane probe or new benchmark substrate of C. glabrata Cdr pumps, and derivative 5 for a new vital dye.

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Section: Synergistic Effect Of Styrylpyridinium Compounds With Antifumentioning

confidence: 99%

Styrylpyridinium Derivatives as New Potent Antifungal Drugs and Fluorescence Probes

et al. 2020

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“…were not satisfactory. Scheid et al (2012) evaluated the combinatory effect of itraconazole or voriconazole with terbinafine or AMB against C. dubliniensis. Treating the yeasts simultaneously with AMB and azole drugs led to a high degree of indifference and antagonism, precluding the use of these substances combined (Scheid et al 2012 C.…”

Section: Introductionmentioning

confidence: 99%

“…Scheid et al (2012) evaluated the combinatory effect of itraconazole or voriconazole with terbinafine or AMB against C. dubliniensis. Treating the yeasts simultaneously with AMB and azole drugs led to a high degree of indifference and antagonism, precluding the use of these substances combined (Scheid et al 2012 C. albicans, C. parapsilosis, C. guilliermondii, C. krusei, C. glabrata, and C. tropicalis. Considering the low number of antifungal drugs available to treat candidiasis and the limited efficacy of combining them to AMB, a feasible strategy to overcome Candida spp.…”

Section: Introductionmentioning

confidence: 99%

Recent developments on the anti-Candida effect of amphotericin B combined with a second drug - a mini-review

MORAES

2023

An. Acad. Bras. Ciênc.

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Invasive Candida infections threaten human health due to the increasing incidence of resistance to the currently available antifungal agents. Amphotericin B (AMB) is the gold standard therapy to treat these infections. Nevertheless, the use of such substance in the clinic is aggravated by its toxicity. Since AMB binds to membrane sterols, it forms pores on human plasma membranes, mainly in kidney cells, leading to nephrotoxicity. The combination of this drug to a second substance could allow for the use of smaller concentrations of AMB, consequently lowering the probability of adverse effects. This mini-review summarizes information regarding an array of substances that enhance AMB antifungal activity. It may be noticed that several of these compounds target plasma membrane. Interestingly, substances approved for human use also presented combinatory anti-Candida activity with AMB. These data reinforce the potential of associating AMB to another drug as a promising therapeutical alternative to treat Candida infections. Further studies, regarding mechanism of action, pharmacokinetics and toxicity parameters must be conducted to confirm the role of these substances as adjuvant agents in candidiasis therapy.

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In vitro activities of antifungal agents alone and in combination against fluconazole-susceptible and -resistant strains of Candida dubliniensis

Cited by 2 publications

References 12 publications

Styrylpyridinium Derivatives as New Potent Antifungal Drugs and Fluorescence Probes

Styrylpyridinium Derivatives as New Potent Antifungal Drugs and Fluorescence Probes

Recent developments on the anti-Candida effect of amphotericin B combined with a second drug - a mini-review

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