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

Cerqueira, Fátima; Medeiros, Rui; Lopes, Inês; Campos, Carla; Ferraz, Maria Pia; Silva, Fernando; Alves, Luís G.; Pinto, Eugénia

doi:10.3390/antibiotics13030222

Cited by 2 publications

(2 citation statements)

References 45 publications

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“…The cyclam salt H 4 [H 2 ( 4-CF3 PhCH 2 ) 2 Cyclam]Cl 4 (compound 1) was previously studied against C. krusei and C. albicans, and demonstrated a relevant antifungal activity, with minimal inhibitory concentration (MIC) values of 8 µg/mL for C. krusei and of 128 µg/mL for C. albicans [7]. More recently, this compound revealed to inhibit biofilm production and catalase activity, being able to interfere with C. albicans dimorphic transition [8]. Given those results, the potential mechanisms involved in the activity of this cyclam derivative were further studied.…”

Section: Discussionmentioning

confidence: 99%

“…The antifungal activity of the cyclam salt H 4 [H 2 ( 4-CF3 PhCH 2 ) 2 Cyclam]Cl 4 (compound 1), depicted in Figure 1, was previously studied by some of us and showed the ability to inhibit the growth of C. krusei and C. albicans [7] and to interfere with the yeasts virulence factors, as catalase activity, biofilm formation and C. albicans dimorphic transition [8].…”

Section: Introductionmentioning

confidence: 99%

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Disclosing the Antifungal Mechanisms of the Cyclam Salt H4[H2(4-CF3PhCH2)2Cyclam]Cl4 against Candida albicans and Candida krusei

Costa,

Lopes,

Morais

et al. 2024

IJMS

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Mycoses are one of the major causes of morbidity/mortality among immunocompromised individuals. Considering the importance of these infections, the World Health Organization (WHO) defined a priority list of fungi for health in 2022 that include Candida albicans as belonging to the critical priority group and Pichia kudriavzevii (Candida krusei) to the medium priority group. The existence of few available antifungal drugs, their high toxicity, the acquired fungal resistance, and the appearance of new species with a broader spectrum of resistance, points out the need for searching for new antifungals, preferably with new and multiple mechanisms of action. The cyclam salt H4[H2(4-CF3PhCH2)2Cyclam]Cl4 was previously tested against several fungi and revealed an interesting activity, with minimal inhibitory concentration (MIC) values of 8 µg/mL for C. krusei and of 128 µg/mL for C. albicans. The main objective of the present work was to deeply understand the mechanisms involved in its antifungal activity. The effects of the cyclam salt on yeast metabolic viability (resazurin reduction assay), yeast mitochondrial function (JC-1 probe), production of reactive oxygen species (DCFH-DA probe) and on intracellular ATP levels (luciferin/luciferase assay) were evaluated. H4[H2(4-CF3PhCH2)2Cyclam]Cl4 induced a significant decrease in the metabolic activity of both C. albicans and C. krusei, an increase in Reactive Oxygen Species (ROS) production, and an impaired mitochondrial function. The latter was observed by the depolarization of the mitochondrial membrane and decrease in ATP intracellular levels, mechanisms that seems to be involved in the antifungal activity of H4[H2(4-CF3PhCH2)2Cyclam]Cl4. The interference of the cyclam salt with human cells revealed a CC50 value against HEK-293 embryonic kidney cells of 1.1 mg/mL and a HC10 value against human red blood cells of 0.8 mg/mL.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Disclosing the Antifungal Mechanisms of the Cyclam Salt H4[H2(4-CF3PhCH2)2Cyclam]Cl4 against Candida albicans and Candida krusei

Costa,

Lopes,

Morais

et al. 2024

IJMS

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Advanced Nanotechnological Approaches for Biofilm Prevention and Control

Ferraz

2024

Applied Sciences

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Biofilm-associated infections present a significant challenge in modern medicine, primarily due to their resilience and resistance to conventional treatments. These infections occur when bacteria form biofilms, protective layers formed by bacterial communities, which are notoriously resistant to traditional antibiotics on surfaces such as medical implants and biological surfaces, making eradication with standard antibiotics difficult. This resilience leads to persistent infections, imposing a substantial economic burden on healthcare systems. The urgency to find alternative treatments is critical as current methods are insufficient and costly. Innovative approaches, such as nanotechnology-based therapies, offer promising alternatives by targeting biofilms more effectively and reducing the need for invasive procedures. Nanocarriers hold significant promise in the fight against biofilm-associated infections. Nanocarriers can penetrate biofilms more effectively than conventional treatments, delivering higher concentrations of antibiotics or other antimicrobial agents precisely where they are needed. This targeted approach not only enhances the efficacy of treatments but also minimizes potential side effects. The development of nanocarrier-based therapies is crucial for overcoming the limitations of current treatments and ultimately improving patient outcomes and reducing the economic burden of biofilm-associated infections on healthcare systems. In this review, nanotechnology-based systems, their characteristics, limitations, and potential benefits are explored to address biofilms-related infections. Additionally, biofilm evaluation models and the tests necessary for the preclinical validation of these nanosystems to facilitate their clinical application are addressed.

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

Cited by 2 publications

References 45 publications

Disclosing the Antifungal Mechanisms of the Cyclam Salt H4[H2(4-CF3PhCH2)2Cyclam]Cl4 against Candida albicans and Candida krusei

Disclosing the Antifungal Mechanisms of the Cyclam Salt H4[H2(4-CF3PhCH2)2Cyclam]Cl4 against Candida albicans and Candida krusei

Advanced Nanotechnological Approaches for Biofilm Prevention and Control

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