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

dc.contributor.authorCosta, Inês
dc.contributor.authorLopes, Inês
dc.contributor.authorMorais, Mariana
dc.contributor.authorSilva, Renata
dc.contributor.authorRemião, Fernando
dc.contributor.authorMedeiros, Rui
dc.contributor.authorAlves, Luís G.
dc.contributor.authorPinto, Eugénia
dc.contributor.authorCerqueira, Fátima
dc.date.accessioned2025-06-20T08:37:51Z
dc.date.available2025-06-20T08:37:51Z
dc.date.issued2024-05-10
dc.description.abstractMycoses 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 μg/mL and a HC10 value against human red blood cells of 0.8 μg/mL.por
dc.description.sponsorshipUIDB/04423/2020, UIDP/04423/2020
dc.identifier.citationCosta, I., Lopes, I., Morais, M., Silva, R., Remião, F., Medeiros, R., Alves, L. G., Pinto, E., & Cerqueira, F. (2024). Disclosing the antifungal mechanisms of the Cyclam Salt H4[H2(4-CF3PhCH2)2Cyclam]Cl4 against Candida albicans and Candida krusei. International Journal of Molecular Sciences, 25(10), Artigo 10. https://doi.org/10.3390/ijms25105209
dc.identifier.doi10.3390/ijms25105209
dc.identifier.eissn1422-0067
dc.identifier.issn1661-6596
dc.identifier.urihttp://hdl.handle.net/10400.22/30166
dc.language.isoeng
dc.peerreviewedyes
dc.publisherMDPI
dc.relationUIDP/00100/2020; UIDB/00100/2020; LA/P/0056/2020;
dc.relation.hasversionhttps://doi.org/10.3390/ijms25105209
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectYeasts
dc.subjectMechanism of action
dc.subjectMetabolic viability
dc.subjectMitochondrial function
dc.subjectCyclam salt
dc.titleDisclosing the antifungal mechanisms of the Cyclam Salt H4[H2(4-CF3PhCH2)2Cyclam]Cl4 against Candida albicans and Candida kruseipor
dc.typeresearch article
dspace.entity.typePublication
oaire.citation.issue10
oaire.citation.titleInternational Journal of Molecular Science
oaire.citation.volume25
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85

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