2-Hydroxychalcone as a Potent Compound and Photosensitizer Against Dermatophyte Biofilms
MetadataShow full item record
Dermatophytes, fungi that cause dermatophytosis, can invade keratinized tissues in humans and animals. The biofilm-forming ability of these fungi was described recently, and it may be correlated with the long treatment period and common recurrences of this mycosis. In this study, we evaluated the anti-dermatophytic and anti-biofilm activity of 2-hydroxychalcone (2-chalcone) in the dark and photodynamic therapy (PDT)-mediated and to determine its mechanism of action. Trichophyton rubrum and Trichophyton mentagrophytes strains were used in the study. The antifungal susceptibility test of planktonic cells, early-stage biofilms, and mature biofilms were performed using colorimetric methods. Topographies were visualized by scanning electron microscopy (SEM). Human skin keratinocyte (HaCat) monolayers were also used in the cytotoxicity assays. The mechanisms of action of 2-chalcone in the dark and under photoexcitation were investigated using confocal microscopy and the quantification of ergosterol, reactive oxygen species (ROS), and death induction by apoptosis/necrosis. All strains, in the planktonic form, were inhibited after treatment with 2-chalcone (minimum inhibitory concentration (MIC) = 7.8-15.6 mg/L), terbinafine (TRB) (MIC = 0.008–0.03 mg/L), and fluconazole (FLZ) (1–512 mg/L). Early-stage biofilm and mature biofilms were inhibited by 2-chalcone at concentrations of 15.6 mg/L and 31.2 mg/L in all tested strains. However, mature biofilms were resistant to all the antifungal drugs tested. When planktonic cells and biofilms (early-stage and mature) were treated with 2-chalcone-mediated PDT, the inhibitory concentrations were reduced by four times (2–7.8 mg/L). SEM images of biofilms treated with 2-chalcone showed cell wall collapse, resulting from a probable extravasation of cytoplasmic content. The toxicity of 2-chalcone in HaCat cells showed higher IC50 values in the dark than under photoexcitation. Further, 2-chalcone targets ergosterol in the cell and promotes the generation of ROS, resulting in cell death by apoptosis and necrosis. Overall, 2-chalcone-mediated PDT is a promising and safe drug candidate against dermatophytes, particularly in anti-biofilm treatment.
How to cite this document
Showing items related by title, author, creator and subject.
Pinho, Sheila Zambello de ; Oliveira, José Brás Barreto de ; Gazola, Rodrigo José Cristiano ; Mazotti, Adriano César ; Molero, Camila Schimite ; Mendes, Carolina Borghi ; Mello, Denise Fernandes de ; Marques, Emilia de Mendonça Rosa ; Talamoni, Jandira Liria Biscalquini ; Silva, José Humberto Dias da et al. (Coleção PROGRAD (UNESP), 2011) [Livro]
Pinho, Sheila Zambello de ; Oliveira, José Brás Barreto de ; Pontes, Sueli Rodrigues ; Almeida, Djanira Soares de Oliveira e ; Godoy, Kathya Maria Ayres de ; Rosa, Claudia de Souza ; Nunes, Julianus Araújo ; Salvador, Sérgio Azevedo ; David, Célia Maria ; Vilche Peña, Angel Fidel et al. (Coleção PROGRAD (UNESP), 2011) [Livro]
Pinho, Sheila Zambello de ; Spazziani, Maria de Lourdes ; Mendonça, Sueli Guadelupe de Lima ; Rubo, Elisabete Aparecida Andrello ; Villarreal, Dalva Maria de Oliveira ; Duarte, Camila ; Okamoto, Mary Yoko ; Souza, Thais R. ; Garms, Gilza Maria Zauhy ; Marin, Fátima Aparecida Dias Gomes et al. (Coleção PROGRAD (UNESP), 2012) [Livro]