Candida albicans growth and germ tube formation can be inhibited by simple diphenyl diselenides [(PhSe)2, (MeOPhSe)2, (p-Cl-PhSe)2, (F3CPhSe)2] and diphenyl ditelluride

Abstract

Candida species are the fourth most common cause of nosocomial bloodstream infections. An increase in the frequency of infections, which have become refractory to standard antifungal therapy, has been observed. Recent studies have shown that the pro-oxidant properties of diphenyl diselenide (PhSe)(2), a structurally simple organoselenium compound, can be toxic to yeast. The objective of this work was to study, under non-reactive oxygen species (ROS)-generating conditions, the effect of different organochalcogenide compounds [(PhSe)(2), (PhTe)(2), (MeOPhSe)(2), (p-Cl-PhSe)(2) and (F(3)CPhSe)(2)] on growth and germ tube formation by Candida albicans. A decrease in C. albicans growth in the presence of crescent concentrations of (PhSe)(2), (PhTe)(2) and (MeOPhSe)(2) was observed. The organochalcogenide compound concentration needed to inhibit 50% (IC50) of the Candida growth was 0.5-2 and 2-10 μmol l(-1), at a cell density of 10(5) and 10(6) cells ml(-1), respectively. The compounds (p-Cl-PhSe)(2) and (F(3)CPhSe)(2) were able to inhibit the cell growth, although the inhibition was considerably weaker than that by (PhSe)(2), (PhTe)(2) and (MeOPhSe)(2). In Candida suspensions incubated in a medium containing serum as an inducer of germ tube formation, the presence of either (PhSe)(2) or (MeOPhSe)(2) at 10 μmol l(-1) completely inhibited the number of cells which formed germ tubes. These results demonstrate the potential of organochalcogenide compounds to inhibit both C. albicans growth and germ tube formation.

Reaction of bis[(2-chlorocarbonyl)phenyl] Diselenide with Phenols, Aminophenols, and Other Amines towards Diphenyl Diselenides with Antimicrobial and Antiviral Properties

“…The probable lack of inhibitory effect of the majority of compounds tested might be due to the fact that the antifungal activity of diphenyl diselenides is dependent on the presence of functional groups [ 40 ]. However, diphenyl diselenides may still display high activity in reducing germ tube formation, one of the crucial virulent factors of C. albicans [ 38 ]. Azoles (ketoconazole and itraconazole), commonly used in antifungal therapy, also did not show activity under the test conditions.…”

“…In the context of biological applications, organoselenium compounds have received particular attention as glutathione peroxidase (GPx) mimics [ 9 , 11 , 14 , 24 ], antioxidant, and anti-inflammatory agents [ 10 , 11 , 13 , 23 ]. Furthermore, a number of selenium-containing compounds have been studied as anticancer [ 12 , 22 , 25 ], anti-angiogenic [ 26 ], antiviral [ 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ], antimicrobial [ 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ], and antileishmanial agents [ 47 ].…”

“…The urgent need for the next generation of antimicrobials and antivirals perpetuates research into designing novel molecules and investigating their mechanisms of action. The tremendous efforts in this area has led to the identification of many bioactive structures [ 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ]. Several enzymes, among them thioredoxin reductase [ 36 , 48 ], bacterial urease [ 49 ], and plasma membrane H+-ATPase [ 50 , 51 , 52 ], were suggested as targets for organoselenium compounds with antimicrobial properties.…”

Diphenyl diselenide (PhSe)2 inhibits biofilm formation by Candida albicans, increasing both ROS production and membrane permeability

“…The pro-oxidant effect of the organochalcogenide compound (PhSe) 2 , producing toxic effects on yeast has been demonstrated [33,35]. Recently, it was demonstrated the ability of the organochalcogenide compound (PhSe) 2 to inhibit both growth and germ tube formation by C. albicans [37]. This is an important feature, because the germ tube formation is an essential stage to virulence of C. albicans in animal models of mucosal and systemic infections [39,40].…”

“…It is a very interesting feature that, while (PhSe) 2 has an antioxidant effect, which produce a neuroprotective effect in rats, it can, also, present pro-oxidant properties in different biological systems [36]. Recently, we have demonstrated that different organochalcogenides inhibited both growth and germ tube formation in C. albicans [37]. Accordingly, the antifungal effect of different organochalcogenide compounds against pathogenic fungi was, recently, described [38].…”