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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

2-Hydroxychalcone as a Potent Compound and Photosensitizer Against Dermatophyte Biofilms

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Bila, Niura Madalena [1, 2] ; Costa-Orlandi, Caroline Barcelos [1] ; Vaso, Carolina Orlando [1] ; Bonatti, Jean Lucas Carvalho [1] ; de Assis, Leticia Ribeiro [3] ; Regasini, Luis Octavio [3] ; Fontana, Carla Raquel [1] ; Fusco-Almeida, Ana Marisa [1] ; Mendes-Giannini, Maria Jose Soares [1]
Total Authors: 9
[1] Univ Estadual Paulista UNESP, Sch Pharmaceut Sci, Dept Clin Anal, Araraquara, SP - Brazil
[2] Univ Eduardo Mondlane UEM, Sch Vet, Dept Para Clin, Maputo - Mozambique
[3] Univ Estadual Paulista UNESP, Inst Biosci Humanities & Exact Sci, Dept Chem & Environm Sci, Sao Jose Do Rio Preto - Brazil
Total Affiliations: 3
Document type: Journal article
Web of Science Citations: 2

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. (AU)

FAPESP's process: 18/02785-9 - Dermatophytes and Dermatophytosis: biofilm formation and development of control strategies.
Grantee:Maria José Soares Mendes Giannini
Support Opportunities: Regular Research Grants
FAPESP's process: 19/22188-8 - Evaluation of the interaction of biofilms mono and dual-species of Candida spp and dermatophytes photodynamic therapy combined with 2-chalcone
Grantee:Níura Madalena Bila
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 20/15586-4 - Establishment of a three-dimensional model to determine the pharmacological efficacy and safety of nitrofuran and indoles derivatives and evaluation of Histoplasma capsulatum infection
Grantee:Carolina Orlando Vaso
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 17/18388-6 - Role of biofilm in the pathogenesis of dermatophytosis and development of combat strategies
Grantee:Caroline Barcelos Costa Orlandi
Support Opportunities: Scholarships in Brazil - Post-Doctoral