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https://www.arca.fiocruz.br/handle/icict/46027
EVALUATION OF NEW POTENTIAL COMPOUNDS FOR THE TREATMENT OF CHROMOBLASTOMYCOSIS
Author
Affilliation
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Micologia. Rio de Janeiro, RJ, Brasil.
Stony Brook University. Department of Microbiology and Immunology. New York, NY, USA.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Micologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Micologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de regulação da expressão gênica. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Micologia. Rio de Janeiro, RJ, Brasil.
Stony Brook University. Department of Microbiology and Immunology. New York, NY, USA.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Micologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Micologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de regulação da expressão gênica. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Micologia. Rio de Janeiro, RJ, Brasil.
Abstract
Chromoblastomycosis (CBM) is a chronic fungal infection of the cutaneous and subcutaneous tissue caused by traumatic implantation, had black fungi of several species as etiological agents. This disease is considered an occupational disease that mainly affects professions related to the handling of soil like the agricultural sector, of civil construction, exposed to contaminated vegetable materials. The most common CBM agents are Fonsecaea species, Phialophora verrucosa, Cladophialophora carrionii, Rhinocladiella aquaspersa, Rhinocladiella similis, Exophiala dermatitidis, Exophiala jeanselmei and others. There is no standard of CBM treatment to follow, requiring more than one drug to be administered and physical methods in most cases. Itraconazole (ITZ) and terbinafine (TRB) are the drugs most commonly used. There are few antifungals that can be used in the treatment of CBM, the refractoriness of some cases and potential recurrences this mycosis, a preclinical study involving compounds already established for other diseases and with known cytotoxicity will allow an evaluation of potential new drugs that may be included in clinical trials for the treatment of CBM in the future. Thus, the objective of this study was to evaluate the antifungal activity of 400 molecules present in Pathogen box against CBM agents. The initial screening with Fonsecaea pedrosoi strain highlighted two compounds: MMV021013 and MMV688978 that presented MIC values between 1.25-5µM and 1.25-2.5µM, respectively, against different CBM agents. The in vitro MIC determination was followed by EUCAST protocol. The analysis of potential synergism of these compounds with the drugs already used in the treatment of this disease (ITZ and TRB) was also be performed. Through these results will can to selected compounds that may be used as promising drugs in the treatment or prophylaxis of CBM in the future.
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