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

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.

Copper(II) and Zinc(II) Complexes with the Clinically Used Fluconazole: Comparison of Antifungal Activity and Therapeutic Potential

“…Based on this, the mode of activity could be similar to the one of fluconazole itself, while it is possible that complex 1 is interacting with some additional targets to cause even further decrease in the total amount of ergosterol. These findings are in line with previous results published by Guo et al, which represented the same effect of polyoxovanadate functionalized by zinc(II)-fluconazole complex [ 44 ]. They studied the mechanism of ergosterol biosynthesis reduction by the latter complex by evaluating the expression of five genes involved in ergosterol biosynthesis (ERG1, ERG7, ERG11, ERG27 and ERG28) and showed that this complex may also inhibit the ERG gene expression.…”

“…Both complexes showed the higher activity (2.7-fold improvement; µM) than fluconazole against C. albicans clinical isolates, and the activity decreased in the case of Cu(II) complex 1 against C. albicans and C. krusei type of strains in comparison to that of fluconazole. These findings are in line with the recent study of Guo et al [ 44 ], who reported a new polyoxovanadate functionalized by zinc(II)-fluconazole complex with good activity on several clinical Candida strains. Notably, the complexation of fluconazole with the Cu(II) and Zn(II) ions resulted in the 11.4- to 12.7-fold increased cytotoxicity, however the selectivity indices of each complex were up to 41 and 73 for 1 and 2 , respectively ( Table 1 ).…”

Vanadium: Risks and possible benefits in the light of a comprehensive overview of its pharmacotoxicological mechanisms and multi-applications with a summary of further research trends

“…ergosterol [134] (Fig. 11), by affecting the expression of genes involved in the synthesis of this compound [135] have been suggested. inhibition of the activity of phosphatases [125] (Fig.…”

“…Vanadium against certain viruses, bacteria, parasites, and fungi. Based on available literature data[26,33,39,45,[124][125][126][127][128][129][130][131][132][133][134][135][136][137].…”

Experimental and theoretical insights of functionalized hexavanadates on Na+/K+-ATPase activity; molecular interaction field, ab initio calculations and in vitro assays

“…V10 is known to modulate the activity of many proteins such as phosphatases [32], , myosin [33][34] and calcium pump ATPase [35][36] and to interact with proteins such as actin [26,37,38]. New POVs have antifungal activities against Candida species [39][40].…”