Diphenyl diselenide suppresses key virulence factors of <i>Candida krusei</i>, a neglected fungal pathogen

Silva, Bruna Marques da; Pinto, Ana Paula; Passos, Juliene Cristina da Silva; Rocha, João Batista Teixeira da; Alberto-Silva, Carlos; Costa, Maricília Silva

doi:10.1080/08927014.2022.2084388

Cited by 7 publications

(5 citation statements)

References 49 publications

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“…Small molecules are particularly promising because of their excellent stability, low toxicity, and minimal drug resistance. Notably, maleimide and diselenide scaffolds possess numerous desirable biological properties ( 15 – 17 ). In this study, a novel maleimide-diselenide hybrid (YH7) was successfully synthesized using a facile and metal-free reaction approach.…”

Section: Discussionmentioning

confidence: 99%

“…Selenium-containing compounds participate in biological redox reactions and can inhibit microbial attachment to solid surfaces ( 13 , 14 ). Diphenyl diselenide compounds have been shown to possess anti-inflammatory, antioxidant, and antifungal activities ( 15 , 16 ). Maleimide is an important structural core of the active molecular class of natural marine alkaloids, and extensive research on their derivatives in medicine indicates they have diverse bioactivities ( 17 – 19 ).…”

Section: Introductionmentioning

confidence: 99%

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Novel small-molecule compound YH7 inhibits the biofilm formation of Staphylococcus aureus in a sarX -dependent manner

Xiao,

Wan,

et al. 2024

mSphere

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The emergence of antibiotic-resistant and biofilm-producing Staphylococcus aureus isolates presents major challenges for treating staphylococcal infections. Biofilm inhibition is an important anti-virulence strategy. In this study, a novel maleimide-diselenide hybrid compound (YH7) was synthesized and demonstrated remarkable antimicrobial activity against methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) in both planktonic cultures and biofilms. The minimum inhibitory concentration (MIC) of YH7 for S. aureus isolates was 16 µg/mL. Quantification of biofilms demonstrated that the sub-MIC (4 µg/mL) of YH7 significantly inhibits biofilm formation in both MSSA and MRSA. Confocal laser scanning microscopy analysis further confirmed the biofilm inhibitory potential of YH7. YH7 also significantly suppressed bacterial adherence to A549 cells. Moreover, YH7 treatment significantly inhibited S. aureus colonization in nasal tissue of mice. Preliminary mechanistic studies revealed that YH7 exerted potent biofilm-suppressing effects by inhibiting polysaccharide intercellular adhesin (PIA) synthesis, rather than suppressing bacterial autolysis. Real-time quantitative PCR data indicated that YH7 downregulated biofilm formation-related genes ( clfA , fnbA , icaA, and icaD ) and the global regulatory gene sarX , which promotes PIA synthesis. The sarX -dependent antibiofilm potential of YH7 was validated by constructing S. aureus NCTC8325 sarX knockout and complementation strains. Importantly, YH7 demonstrated a low potential to induce drug resistance in S. aureus and exhibited non-toxic to rabbit erythrocytes, A549, and BEAS-2B cells at antibacterial concentrations. In vivo toxicity assays conducted on Galleria mellonella further confirmed that YH7 is biocompatible. Overall, YH7 demonstrated potent antibiofilm activity supports its potential as an antimicrobial agent against S. aureus biofilm-related infections. IMPORTANCE Biofilm-associated infections, characterized by antibiotic resistance and persistence, present a formidable challenge in healthcare. Traditional antibacterial agents prove inadequate against biofilms. In this study, the novel compound YH7 demonstrates potent antibiofilm properties by impeding the adhesion and the polysaccharide intercellular adhesin production of Staphylococcus aureus . Notably, its exceptional efficacy against both methicillin-resistant and methicillin-susceptible strains highlights its broad applicability. This study highlights the potential of YH7 as a novel therapeutic agent to address the pressing issue of biofilm-driven infections.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Novel small-molecule compound YH7 inhibits the biofilm formation of Staphylococcus aureus in a sarX -dependent manner

Xiao,

Wan,

et al. 2024

mSphere

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“…Additionally, diphenyl diselenide has been associated with inhibiting crucial virulence factors in Candida krusei , specifically impeding adherence to epithelial cells, biofilm formation, and fungal growth. This underscores its potential as an antifungal agent, surpassing the efficacy of p‐chlorophenyl diselenide [359] …”

Section: Pharmacology Of Diorganyl Diselenidesmentioning

confidence: 97%

“…This underscores its potential as an antifungal agent, surpassing the efficacy of p-chlorophenyl diselenide. [359] A selenium-containing azole derivative (1,2-bis(1-(2,4dichlorophenyl)-2-(1H-imidazole-1-yl) ethyl) diselane) exhibited minimal cytotoxicity and hemolysis effects. This azole derivative displayed remarkable efficacy against Candida (Figure 2), including strains resistant to fluconazole.…”

Section: Diorganyl Diselenides As Antimicrobial Agentsmentioning

confidence: 99%

Recent Progress in Synthetic and Biological Application of Diorganyl Diselenides

do Carmo Pinheiro,

Souza Marques,

Ten Kathen Jung

et al. 2024

The Chemical Record

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Diorganyl diselenides have emerged as privileged structures because they are easy to prepare, have distinct reactivity, and have broad biological activity. They have also been used in the synthesis of natural products as an electrophile in the organoselenylation of aromatic systems and peptides, reductions of alkenes, and nucleophilic substitution. This review summarizes the advancements in methods for the transformations promoted by diorganyl diselenides in the main functions of organic chemistry. Parallel, it will also describe the main findings on pharmacology and toxicology of diorganyl diselenides, emphasizing anti‐inflammatory, hypoglycemic, chemotherapeutic, and antimicrobial activities. Therefore, an examination detailing the reactivity and biological characteristics of diorganyl diselenides provides valuable insights for academic researchers and industrial professionals.

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“…The list of C. albicans virulence factors is extensive and includes its capacity for dimorphic transition [ 22 ]. C. krusei , sometimes neglected with respect to C. albicans, is intrinsically resistant to fluconazole and is of clinical interest too [ 21 , 23 ]. C. neoformans is a yeast that accounts for a great number of central nervous system infections, namely in diabetic and immunosuppressed patients.…”

Section: Introductionmentioning

confidence: 99%

A Cyclam Salt as an Antifungal Agent: Interference with Candida spp. and Cryptococcus neoformans Mechanisms of Virulence

Cerqueira,

Medeiros,

Lopes

et al. 2024

Antibiotics

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The importance of fungal infections, particularly those caused by yeasts, is increasing among the medical community. Candida albicans and Cryptococcus neoformans are amongst the high-priority fungal species identified by the World Health Organization (WHO) and are considered in the critical group, while Candida krusei is included in the medium-priority group. The cyclam salt H4[H2(4-CF3PhCH2)2Cyclam]Cl4 proved to be active against the growth of these three yeasts, and the aim of this work was to verify its interference with their virulence mechanisms, whether shared or unique. H4[H2(4-CF3PhCH2)2Cyclam]Cl4 significantly inhibited biofilm production and catalase activity, being able to interfere with C. albicans dimorphic transition and C. neoformans melanin production. At the minimal inhibitory concentration (MIC) values, H4[H2(4-CF3PhCH2)2Cyclam]Cl4 had no antioxidant effect, as determined by the DPPH method. When using the RAW264.7 macrophage cell line, H4[H2(4-CF3PhCH2)2Cyclam]Cl4 reduced nitric oxide (NO) detection (the Griess reaction), but this effect was associated with a significant toxic effect on the cells.

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Diphenyl diselenide suppresses key virulence factors of Candida krusei, a neglected fungal pathogen

Cited by 7 publications

References 49 publications

Novel small-molecule compound YH7 inhibits the biofilm formation of Staphylococcus aureus in a sarX -dependent manner

Novel small-molecule compound YH7 inhibits the biofilm formation of Staphylococcus aureus in a sarX -dependent manner

Recent Progress in Synthetic and Biological Application of Diorganyl Diselenides

A Cyclam Salt as an Antifungal Agent: Interference with Candida spp. and Cryptococcus neoformans Mechanisms of Virulence

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