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Investigation of curcumin analogues as agents against fungi that caused dermatological mycoses

Grant number: 18/08994-9
Support type:Scholarships in Brazil - Master
Effective date (Start): August 01, 2018
Effective date (End): February 29, 2020
Field of knowledge:Biological Sciences - Microbiology
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Luis Octávio Regasini
Grantee:Veridianna Camilo Pattini
Home Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil

Abstract

Superficial and cutaneous mycoses are fungal infections that affect the outer layer of the stratum corneum of the skin and its attachments. They are the most numerous and widespread group of all mycoses, affecting all age groups. Negative aesthetics is the first impact of superficial and cutaneous mycoses. However, these mycoses are not restricted to the aesthetic aspect, becoming a health problem in the neonatal, senescent and immunocompromised population groups. Dermatomycosis on these patients can progress to systemic infections and become lethal. At this point, the arsenal of antifungal agents is extremely limited, since most of drugs belong to a few classes with limited mechanism of action. Moreover, many drugs exhibit high toxicity, drug interactions and a high economic cost. Relapses through conventional treatment are often frequent, which are caused by resistant strains. This scenario lead us to search innovative antifungals for treatment of fungal infections. The major aim of this project proposal is to investigate curcumin analogues (curcuminoids) as agents against fungi that caused dermatological mycoses, including dermatophytes, Candida spp. and filamentous non-dermatophytes (Fusarium sp.). Some of these analogues, part of our research, showed activity against Candida albicans, which exhibited the MIC value lower than 4,0 µg/mL. The curcuminoids will have their antifungal potential and their toxicity evaluated by the following tests: a) fungal susceptibility, using reference strains (ATCC) and clinical isolates from Base Hospital of São José do Rio Preto - São Paulo; b) antifungal activity of selected curcuminoids in combination with antifungal drugs fluconazole and terbinafine by the checkerboard method; c) growth inhibition of Candida albicans hyphae; d) Time -kill assay; e) anti-biofilm of C. albicans; f) cytotoxicity against human keratinocytes (HaCaT); g) Acute toxicity against Galleria Mellonella, selected as alternative model for in vivo assays.