Investigação de análogos de curcumina como agentes contra fungos causadores de dermatomicoses
Carregando...
Data
2020-03-27
Autores
Pattini, Veridianna Camilo
Título da Revista
ISSN da Revista
Título de Volume
Editor
Universidade Estadual Paulista (Unesp)
Resumo
As micoses superficiais e cutâneas são infecções fúngicas que acometem a camada mais externa do estrato córneo da pele e seus anexos. São as micoses mais frequentes dentre todas as infecções fúngicas e estão distribuídas por todo o mundo, afetando todas as faixas etárias. O impacto primário destas micoses é seu aspecto visual com estética negativa. Contudo, não se restringem apenas ao aspecto estético, vindo a ser um grave problema de saúde na população neonatal, senescente e de imunocomprometidos. Além disso, muitos fármacos exibem toxicidade alta, interações medicamentosas e alto custo econômico. As recidivas por meio do tratamento convencional costumam ser frequentes, as quais podem ser ocasionadas por cepas resistentes. Esse cenário torna premente a busca por antifúngicos inovadores. No presente estudo avaliou-se atividade antifúngica de 19 curcuminoides, provenientes da composteca do Laboratório de Antibióticos e Quimioterápicos (LAQ), contra fungos filamentosos dermatofíticos dos gêneros Trichophyton, Epidermophyton e Microsporum e leveduriformes (Candida spp.), de cepas de referência ATCC e de isolados clínicos, provenientes da coleção do Laboratório de Microbiologia da Faculdade de Medicina de São José do Rio Preto (FAMERP), bem como avaliou-se toxicidade dos curcuminoides mais potentes contra células de queratinócitos humanos (HaCat) e larva G. mellonella. Afim de verificar a atividade antifúngica dos compostos, foram determinados os valores: Concentração Inibitória Mínima (CIM) e Concentração Fungicída Mínima (CFM); ensaio de atividade combinatória dos curcuminoides e fluconazol, para Candida tropicalis e terbinafina, para as espécies de dermatófitos e ensaios de inibição de desenvolvimento hifal. Seis curcuminoides apresentaram inibição maior que 50% em mais de uma cepa dentre as testadas. Os valores de CIM variaram de 1,9 a 31,2 µg/mL. O curcuminoide 2 (DMC), foi o composto mais promissor da série, apresentou atividade antifúngica contra linhagens de cepa de origem clínica de T. rubrum, T. mentagrophytes, E. floccosum e cepas referência de T. rubrum CBS 118892 e C. tropicalis ATCC 13803; efeito sinérgico em combinação com a terbinafina contra E. floccosum e efeito inibitório do desenvolvimento de hifal da C. tropicalis. DMC apresentou baixa toxicidade contra células HaCat nas concentração do CIM e não apresentou toxicidade na concentração de 125 µg/mL (3 ×CIM) contra G. mellonella, o que o torna um composto promissor para abordagens terapêuticas no controle de dermatomicoses.
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.
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.
Descrição
Palavras-chave
Curcumina, Curcuminoides, Atividade antifúngica, Micoses, Dermatófitos, Candida sp, Curcumin, Curcuminoids, Antifungal activity, Mycoses, Dermatophytes