Antifungal activities of diphenyl diselenide and ebselen alone and in combination with antifungal agents againstFusariumspp.

Abstract

Herein, we describe the in vitro activity of a combination of the organoselenium compounds diphenyl diselenide and ebselen alone and in combination with amphotericin B, caspofungin, itraconazole, and voriconazole against 25 clinical isolates of Fusarium spp. For this analysis, we used the broth microdilution method based on the M38-A2 technique and checkerboard microdilution method. Diphenyl diselenide (MIC range = 4-32 μg/ml) and ebselen (MIC range = 2-8 μg/ml) showed in vitro activity against the isolates tested. The most effective combinations were (synergism rates): ebselen + amphotericin B (88%), ebselen + voriconazole (80%), diphenyl diselenide + amphotericin B (72%), and diphenyl diselenide + voriconazole (64%). Combination with caspofungin resulted in low rates of synergism: ebselen + caspofungin, 36%, and diphenyl diselenide + caspofungin, 28%; combination with itraconazole demonstrated indifferent interactions. Antagonistic effects were not observed for any of the combinations tested. Our findings suggest that the antifungal potential of diphenyl diselenide and ebselen deserves further investigation in in vivo experimental models, especially in combination with amphotericin B and voriconazole.

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

“…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.…”

Allylic Selenocyanates as New Agents to Combat Fusarium Species Involved with Human Infections

“…Ebselen and diselenides have demonstrated activity against Fusarium sp. when administrated alone or in combination with other antifungal drugs showing good synergistic effects ,. It was shown that a piperidine isoselenocyanate derivative is the most active among its isosters against selected fungi, including Fusarium culmorum .…”

In vitro combination between antifungals and diphenyl diselenide against Cryptococcus species

“…Alone, this compound has antimicrobial activity against pathogenic bacteria, fungi, oomycetes ( Pythium insidiosum ) and antiviral action on Herpes simplex virus 2 infection . Interestingly, this compound interacted synergistically with antifungal drugs against Candida glabrata , Sporothrix brasiliensis and Fusarium spp . However, activity of the (PhSe) 2 was not investigated against Cryptococcus spp.…”