Antifungal Activity of the Biphosphinic Cyclopalladate C7a against Candida albicans Yeast Forms In Vitro and In Vivo

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dc.citation.volume8
dc.contributor.authorMunoz, Julian E.
dc.contributor.authorRossi, Diego C. P.
dc.contributor.authorIshida, Kelly
dc.contributor.authorSpadari, Cristina C.
dc.contributor.authorMelhem, Marcia S. C.
dc.contributor.authorGarcia, Daniel M. [UNIFESP]
dc.contributor.authorCaires, Antonio C. F.
dc.contributor.authorTaborda, Carlos P.
dc.contributor.authorRodrigues, Elaine G. [UNIFESP]
dc.coverageLausanne
dc.date.accessioned2020-07-13T11:53:14Z
dc.date.available2020-07-13T11:53:14Z
dc.date.issued2017
dc.description.abstractVulvovaginal and invasive candidiasis are frequent conditions in immunosuppressed individuals caused by Candida albicans and non-albicans Candida spp. Fluconazole and Amphotericin B are the main drugs used to fight the infection. However, resistance to fluconazole and other azole antifungal drugs is an important clinical problem that encourages the search for new therapeutic alternatives. In this work, we evaluate the antifungal activity of the biphosphinic cyclopalladate C7a in the in vitro and in vivo model. Our results showed fungicidal activity, with low values of minimal inhibitory concentrations and minimum fungicidal concentrations, even for fluconazole and/or miconazole resistant Candida isolates. Fluorescence microscopy and transmission electron microscopy revealed that the compound was able to inhibit the formation of hyphae/pseudohyphae and, moreover, promoted morphological alterations in cellular organelles and structures, such as disruption of cell wall, apparent mitochondrial swelling, chromatin marginalization into the nuclei and increased numbers of electronlucent vacuoles. C7a significantly decreased the biofilm formation and reduced the viability of yeast cells in mature biofilms when tested against a virulent C. albicans strain. In vivo assays demonstrated a significant decrease of fungal burden in local (vaginal canal) and disseminated (kidneys) infection. In addition, we observed a significant increase in the survival of the systemically infected animals treated with C7a. Our results suggest C7a as a novel therapeutic agent for vaginal and disseminated candidiasis, and an alternative for conventional drug-resistant Candida.en
dc.description.affiliationUniv Sao Paulo, Dept Microbiol, Biomed Sci Inst, Sao Paulo, Brazil
dc.description.affiliationColegio Mayor Cundinamarca Univ, Fac Hlth Sci, Bogota, Colombia
dc.description.affiliationAdolfo Lutz Inst, Parasitol Sect, Tech Div Med Biol, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Pharmacol, Sao Paulo, Brazil
dc.description.affiliationUniv Mogi das Cruzes, Interdisciplinary Ctr Biochem Invest, Mogi Das Cruzes, Brazil
dc.description.affiliationUniv Sao Paulo, Lab Med Mycol IMTSP LIM53, Sao Paulo, Brazil
dc.description.affiliationFed Univ Sao Paulo EPM UNIFESP, Dept Microbiol Immunol & Parasitol, Paulista Sch Med, Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Pharmacol, Sao Paulo, Brazil
dc.description.affiliationUnifespFed Univ Sao Paulo EPM UNIFESP, Dept Microbiol Immunol & Parasitol, Paulista Sch Med, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipCAPES
dc.description.sponsorshipFAPESP
dc.description.sponsorshipCNPq
dc.description.sponsorshipIDCAPES: 88881.062125/2014-01
dc.description.sponsorshipIDFAPESP: 2013/18655-3
dc.description.sponsorshipIDFAPESP: 2012/08760-1
dc.format.extent-
dc.identifierhttp://dx.doi.org/10.3389/fmicb.2017.00771
dc.identifier.citationFrontiers In Microbiology. Lausanne, v. 8, p. -, 2017.
dc.identifier.doi10.3389/fmicb.2017.00771
dc.identifier.fileWOS000400544700001.pdf
dc.identifier.issn1664-302X
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/54472
dc.identifier.wosWOS:000400544700001
dc.language.isoeng
dc.publisherFrontiers Media Sa
dc.relation.ispartofFrontiers In Microbiology
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectCandida spp.en
dc.subjectclinical isolatesen
dc.subjectantifungal chemotherapyen
dc.subjectcyclopalladated C7aen
dc.subjectvaginal candidiasisen
dc.subjectdisseminated candidiasisen
dc.subjectdrug-resistant yeasten
dc.titleAntifungal Activity of the Biphosphinic Cyclopalladate C7a against Candida albicans Yeast Forms In Vitro and In Vivoen
dc.typeinfo:eu-repo/semantics/article
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