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

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY; v. 11, MAY 13 2021.
• Citações Web of Science: 2

Resumo

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)

• Processo FAPESP: 18/02785-9 - Dermatófitos e Dermatofitoses: formação de biofilme e desenvolvimento de estratégias de controle.
• Beneficiário: Maria José Soares Mendes Giannini
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 19/22188-8 - Avaliação da interação de biofilmes mono e dual-espécies de Candida spp e dermatófitos combinada a terapia fotodinâmica com 2-chalcona
• Beneficiário: Níura Madalena Bila
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 20/15586-4 - Estabelecimento de um modelo tridimensional para determinação da eficácia e segurança farmacológica de derivados de nitrofuranos e indólicos e avaliação da infecção de Histoplasma capsulatum
• Beneficiário: Carolina Orlando Vaso
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 17/18388-6 - O papel do biofilme na patogênese das dermatofitoses e desenvolvimento de estratégias de combate
• Beneficiário: Caroline Barcelos Costa Orlandi
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado