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In vitro and in vivo antifungal activities and mechanism of heteropolytungstates against Candida species
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In vitro and in vivo antifungal activities and mechanism of heteropolytungstates against Candida species
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Journal Article
In vitro and in vivo antifungal activities and mechanism of heteropolytungstates against Candida species
2017
Overview
The antifungal activities of heteropolytungstates, α-1,2,3-K
6
H[SiW
9
V
3
O
40
] (SiW-3), K
13
[Ce(SiW
11
O
39
)
2
]·17H
2
O (SiW-5), K
13
[Eu(SiW
11
O
39
)
2
]·25H
2
O (SiW-10), K
6
PV
3
W
9
O
40
(PW-6), α-K
4
PVW
11
O
40
(PW-8), were screened in 29
Candida albicans
, 8
Candida glabrata
, 3
Candida krusei
, 2
Candida parapsilosis
, 1
Candida tropicalis
, and 1
Cryptococcus neoformans
strains using the CLSI M27-A3 method. SiW-5 had the highest efficacy with a minimum inhibitory concentration (MIC) values of <0.2–10.2
μ
M
in vitro
. The antifungal mechanism, acute toxicity and
in vivo
antifungal activity of SiW-5 were then evaluated in
C. albicans
. The results showed that SiW-5 damaged the fungal cell membrane, reduce the ergosterol content and its main mode of action was through inhibition of ergosterol biosynthesis. Real-time PCR showed that ERG1, ERG7, ERG11 and ERG28 were all significantly upregulated by SiW-5. An acute toxicity study showed the 50% lethal dose (LD
50
) of SiW-5 for ICR mice was 1651.5 mg/kg. And
in vivo
antifungal studies demonstrated that SiW-5 reduced both the morbidity and fungal burden of mice infected with
C. albicans
. This study demonstrates that SiW-5 is a potential antifungal candidate against the
Candida
species.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Animals
/ Antifungal Agents - adverse effects
/ Antifungal Agents - chemistry
/ Antifungal Agents - pharmacology
/ Candida
/ Candida albicans - drug effects
/ Candida albicans - pathogenicity
/ Candida albicans - ultrastructure
/ Chromatography, High Pressure Liquid
/ Drug Evaluation, Preclinical
/ Humanities and Social Sciences
/ Microscopy, Electron, Transmission
/ Minimum inhibitory concentration
/ Real-Time Polymerase Chain Reaction
/ Science
/ Toxicity
/ Transmission electron microscopy
