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Membranolytic Activity Profile of Nonyl 3,4-Dihydroxybenzoate: A New Anti-Biofilm Compound for the Treatment of Dermatophytosis

dc.contributor.authorCosta-Orlandi, Caroline B. [UNESP]
dc.contributor.authorBila, Níura M. [UNESP]
dc.contributor.authorBonatti, Jean Lucas C. [UNESP]
dc.contributor.authorVaso, Carolina O. [UNESP]
dc.contributor.authorSantos, Mariana B. [UNESP]
dc.contributor.authorPolaquini, Carlos R. [UNESP]
dc.contributor.authorSantoni Biasioli, Mariana M. [UNESP]
dc.contributor.authorHerculano, Rondinelli D. [UNESP]
dc.contributor.authorRegasini, Luis O. [UNESP]
dc.contributor.authorFusco-Almeida, Ana Marisa [UNESP]
dc.contributor.authorMendes-Giannini, Maria José S. [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.contributor.institutionUniversidade Estadual de Maringá (UEM)
dc.date.accessioned2023-07-29T13:56:52Z
dc.date.available2023-07-29T13:56:52Z
dc.date.issued2023-05-01
dc.description.abstractThe ability of dermatophytes to live in communities and resist antifungal drugs may explain treatment recurrence, especially in onychomycosis. Therefore, new molecules with reduced toxicity that target dermatophyte biofilms should be investigated. This study evaluated nonyl 3,4-dihydroxybenzoate (nonyl) susceptibility and mechanism of action on planktonic cells and biofilms of T. rubrum and T. mentagrophytes. Metabolic activities, ergosterol, and reactive oxygen species (ROS) were quantified, and the expression of genes encoding ergosterol was determined by real-time PCR. The effects on the biofilm structure were visualized using confocal electron microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). T. rubrum and T. mentagrophytes biofilms were susceptible to nonyl and resistant to fluconazole, griseofulvin (all strains), and terbinafine (two strains). The SEM results revealed that nonyl groups seriously damaged the biofilms, whereas synthetic drugs caused little or no damage and, in some cases, stimulated the development of resistance structures. Confocal microscopy showed a drastic reduction in biofilm thickness, and transmission electron microscopy results indicated that the compound promoted the derangement and formation of pores in the plasma membrane. Biochemical and molecular assays indicated that fungal membrane ergosterol is a nonyl target. These findings show that nonyl 3,4-dihydroxybenzoate is a promising antifungal compound.en
dc.description.affiliationDepartment of Clinical Analysis School of Pharmaceutical Sciences São Paulo State University (U.N.E.S.P.), SP
dc.description.affiliationDepartment of Para-Clinic School of Veterinary Eduardo Modlane University (UEM)
dc.description.affiliationDepartment of Chemistry and Environmental Sciences Institute of Biosciences Humanities and Exact Sciences São Paulo State University (U.N.E.S.P.), SP
dc.description.affiliationDepartment of Biological Sciences School of Pharmaceutical Sciences São Paulo State University (U.N.E.S.P.), SP
dc.description.affiliationDepartment of Bioprocesses and Biotechnology School of Pharmaceutical Sciences São Paulo State University (U.N.E.S.P.), SP
dc.description.affiliationUnespDepartment of Clinical Analysis School of Pharmaceutical Sciences São Paulo State University (U.N.E.S.P.), SP
dc.description.affiliationUnespDepartment of Chemistry and Environmental Sciences Institute of Biosciences Humanities and Exact Sciences São Paulo State University (U.N.E.S.P.), SP
dc.description.affiliationUnespDepartment of Biological Sciences School of Pharmaceutical Sciences São Paulo State University (U.N.E.S.P.), SP
dc.description.affiliationUnespDepartment of Bioprocesses and Biotechnology School of Pharmaceutical Sciences São Paulo State University (U.N.E.S.P.), SP
dc.identifierhttp://dx.doi.org/10.3390/pharmaceutics15051402
dc.identifier.citationPharmaceutics, v. 15, n. 5, 2023.
dc.identifier.doi10.3390/pharmaceutics15051402
dc.identifier.issn1999-4923
dc.identifier.scopus2-s2.0-85160438051
dc.identifier.urihttp://hdl.handle.net/11449/248900
dc.language.isoeng
dc.relation.ispartofPharmaceutics
dc.sourceScopus
dc.subjectanti-biofilm activity
dc.subjectantifungal drugs
dc.subjectbiofilms
dc.subjectdermatophytes
dc.subjectmechanism of action
dc.subjectRT-PCR
dc.titleMembranolytic Activity Profile of Nonyl 3,4-Dihydroxybenzoate: A New Anti-Biofilm Compound for the Treatment of Dermatophytosisen
dc.typeArtigo
unesp.author.orcid0000-0002-5752-6367[1]
unesp.author.orcid0000-0002-4236-3366[2]
unesp.author.orcid0000-0002-4629-680X[4]
unesp.author.orcid0000-0001-5913-0246[6]
unesp.author.orcid0000-0002-8059-0826[11]
unesp.departmentAnálises Clínicas - FCFpt
unesp.departmentCiências Biológicas - FCFpt

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