Investigation of curcumin analogs as agents against fungi that cause dermatomycoses

Author(s)

Veridianna Camilo Pattini

• Document type: Master's Dissertation
• Press: São José do Rio Preto. 2020-05-12.
• Institution: Universidade Estadual Paulista (Unesp). Instituto de Biociências Letras e Ciências Exatas. São José do Rio Preto
• Defense date: 2020-03-27
• Advisor: Luis Octavio Regasini; Margarete Teresa Gottardo de Almeida

Abstract

Superficial and cutaneous mycoses are fungal infections that affect the outermost layer of the stratum corneum of the skin and its attachments. They are the most frequent mycoses among all fungal infections and are distributed all over the world. The first impact of these mycoses is their visual appearance with a negative aesthetic. However, they are not restricted to the aesthetic aspect, becoming a serious health problem in the neonatal, senescent and immunocompromised population. In addition, many drugs exhibit high toxicity, drug interactions and high economic cost. Relapses through conventional treatment are often frequent, which can be caused by resistant strains. This scenario demands the development of potent but safer compounds. Herein, we described the antifungal activity of a novel curcuminoid against dermatophyte and Candida species. A series of nineteen curcuminoid analogs was submitted to antifungal assay to assess MIC (minimum inhibitory concentration) and MFC (minimum fungicidal concentration) determined by the broth microdilution method. First, all compound were tested at 31.2 µg mL-1 in order to select the most active compound. The compound 3, 3'-Dimethoxycurcumin (DMC) showed the highest growth-inhibitory activity the largest spectrum of action against dermatophyte clinical isolates and reference strains of Candida tropicalis ATCC and Trichophyton rubrum CBS, with MIC values range of 1.9±31.2 µg mL-1. DMC exhibited fungistatic activity. Inverted microscope indicated C. tropicalis hyphal growth was completely inhibited by DMC. We also found that DMC demonstrated low toxicity against human keratinocyte cells and has no toxicity against Galleria mellonella larvae. DMC antifungal activities against Candida spp. and dermatophytes, and antibiofilm formation activity against C. tropicalis. In addition, DMC was selective to fungal cells compared to human keratinocytes cells. (AU)

• FAPESP's process: 18/08994-9 - Investigation of curcumin analogues as agents against fungi that caused dermatological mycoses
• Grantee: Veridianna Camilo Pattini
• Support Opportunities: Scholarships in Brazil - Master