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Published on: February 14, 2018
In vitro anti-Cryptococcus activity of diphenyl diselenide alone and in combination with amphotericin B and
Jéssica Louise Benelli1,2,3, Vanice Rodrigues Poester1,2, Lívia Silveira Munhoz1,2
1Mycology Laboratory, College of Medicine, Federal University of Rio Grande, Campus Saúde, Visconde de Paranaguá 102, Centro, Rio Grande, Rio Grande do Sul, 96201-900, Brazil.
Abstract:
Cryptococcus is an encapsulated yeast that causes fungal meningitis, most commonly in HIV patients, with high mortality rates. Thus, the study of new treatment options is relevant. Antifungal activity of organoselenium compounds attributed to their pro-oxidative effect in fungal cells has been shown given that few data regarding its anti-Cryptococcus activity are available, this in vitro study was conducted with 40 clinical isolates of Cryptococcus neoformans. Diphenyl diselenide (DD) alone, and its interaction with amphotericin B or fluconazole, was tested by microdilution and checkerboard assays. All Cryptococcus neoformans were inhibited by DD in concentrations ≤ 32 μg/mL, and fungicidal concentrations were ≤ 64 μg/mL. Advantageous interaction between fluconazole occurred in 40% of the isolates, respectively. This study contributes with data of DD alone and in combination with classical drugs of choice for cryptococcosis treatment. Further studies focused on DD antifungal mechanism of action, and in vivo experiments are necessary.
Insights
Diphenyl diselenide (DD) shows promising antifungal activity against Cryptococcus neoformans, inhibiting fungal growth and demonstrating fungicidal effects. This organoselenium compound also shows synergistic potential when combined with fluconazole for treating fungal meningitis.
Area of Science:
- Mycology
- Infectious Diseases
- Pharmacology
Background:
- Cryptococcus is a yeast causing life-threatening fungal meningitis, particularly in HIV patients.
- High mortality rates necessitate novel therapeutic strategies for cryptococcosis.
- Organoselenium compounds exhibit antifungal properties, but their efficacy against Cryptococcus is underexplored.
Purpose of the Study:
- To evaluate the in vitro antifungal activity of diphenyl diselenide (DD) against Cryptococcus neoformans.
- To investigate the potential synergistic interactions between DD and conventional antifungal drugs (amphotericin B, fluconazole).
Main Methods:
- In vitro study utilizing 40 clinical isolates of Cryptococcus neoformans.
- Microdilution and checkerboard assays were employed to determine minimum inhibitory and fungicidal concentrations.
- Tested DD alone and in combination with amphotericin B and fluconazole.
Main Results:
- Diphenyl diselenide (DD) inhibited all Cryptococcus neoformans isolates at concentrations ≤32 μg/mL.
- Fungicidal concentrations of DD were found to be ≤64 μg/mL.
- An advantageous interaction between DD and fluconazole was observed in 40% of the isolates.
Conclusions:
- Diphenyl diselenide (DD) possesses significant in vitro antifungal activity against Cryptococcus neoformans.
- DD demonstrates potential as a standalone agent or in combination therapy for cryptococcosis.
- Further research into DD's mechanism of action and in vivo efficacy is warranted.
