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. 2018 May 9;23(5):1122.
doi: 10.3390/molecules23051122.

In Vitro Anticandidal Activity and Mechanism of a Polyoxovanadate Functionalized by Zn-Fluconazole Complexes

Shuanli Guo  1 , Wei Yang  2 , Mingming Zhao  3 , Rui Tian  4 , Boyu Zhang  5 , Yanfei Qi  6
Affiliations

In Vitro Anticandidal Activity and Mechanism of a Polyoxovanadate Functionalized by Zn-Fluconazole Complexes

Shuanli Guo et al. Molecules. .

Abstract

The rise in the number of fungal infections is requiring the rapid development of novel antifungal agents. A new polyoxovanadate functionalized by Zn-fluconazole coordination complexes, Zn₃(FLC)₆V10O28·10H₂O (ZnFLC) (FLC = fluconazole) has been synthesized and evaluated for in vitro antifungal against Candida species. The identity of ZnFLC were confirmed by elemental analysis, IR spectrum, and single-crystal X-ray diffraction. The antifungal activities of ZnFLC was screened in 19 Candida species strains using the microdilution checkerboard technique. The minimum inhibitory concentration (MIC80) value of ZnFLC is 4 μg/mL on the azole-resistant clinical isolates of C. albicans HL973, which is lower than the positive control, FLC. The mechanism of ZnFLC against C. albicans HL973 showed that ZnFLC damaged the fungal cell membrane and reduced the ergosterol content. The expression of ERG1, ERG7, ERG11 ERG27, and ERG28, which have effects on the synthesis of ergosterol, were all significantly upregulated by ZnFLC.

Keywords: antifungal activity; ergosterol; fluconazole; polyoxovanadate; rt-PCR.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Combined ball-stick and polyhedral representation of 1. The VO6octahedra are shown in green and the balls represent Zinc (light blue), carbon (black), nitrogen (blue), and oxygen (red).
Figure 2
Figure 2
Inhibitory effect of ZnFLC and FLC on HL973 in different doses by MTX assay. Data are presented as the mean ± SD of three independent experiments. (* p < 0.05 for the ZnFLC or FLC vs. DMSO control.)
Figure 3
Figure 3
Inhibitory effect of ZnFLC and on HL973 in different time and different doses. Data are presented as the mean ± SD of three independent experiments.
Figure 4
Figure 4
Fluorescent microscopy of HL973 cells treated with 64 μg/mL of ZnFLC and equivalent dose of FLC in ZnFLC (wt/wt %) at 24 h stained with AO (red) and EB (green). Scale bar: 30 μm.
Figure 5
Figure 5
Concentration changes of ergosterol in C. albicans HL973 treated with 16 μg/mL of ZnFLC and equivalent dose of FLC in ZnFLC (wt/wt %) of FLC at 24 h using HPLC method. The experiment was performed in triplicate. Data were represented as mean ± SD. * p < 0.05 for the ZnFLC or FLC vs. DMSO control. # p < 0.05 for the ZnFLC vs. FLC at MIC.
Figure 6
Figure 6
Expression of ERG genes is increased in clinical isolates HL973. RT-PCR was performed using RNA extracted from cells grown for 24 h treated with 2MIC80 ZnFLC. All data are normalized to an internal control and are expressed as fold induction relative to the expression level in strain. (** p < 0.01 for the ZnFLC vs. DMSO control.)
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