Nívea Pereira de Sá1, Lídia Fátima José de Paula1, Larissa Ferreira Finamore Lopes1, Lana Ivone Barreto Cruz1, Thelma Tirone Silvério Matos1, Cleudiomar Inácio Lino2, Renata Barbosa de Oliveira2, Elaine Maria de Souza-Fagundes3, Beth Burgwyn Fuchs4, Eleftherios Mylonakis4, Susana Johann5. 1. Department of Microbiology, Institute of Biological Sciences, University Federal of Minas Gerais, Av. Antônio Carlos 6627, P.O. Box 486, 31270-901 Belo Horizonte, MG, Brazil. 2. Department of Pharmaceutical Products, Pharmacy School of UFMG, University Federal of Minas Gerais, Belo Horizonte, MG, Brazil. 3. Department of Physiology and Biophysics, Institute of Biological Sciences, University Federal of Minas Gerais, Belo Horizonte, MG, Brazil. 4. Division of Infectious Diseases, Rhode Island Hospital, Alpert Medical School, and Brown University, Providence, RI, USA. 5. Department of Microbiology, Institute of Biological Sciences, University Federal of Minas Gerais, Av. Antônio Carlos 6627, P.O. Box 486, 31270-901 Belo Horizonte, MG, Brazil. Electronic address: sjohann@icb.ufmg.br.
Abstract
OBJECTIVES: Candida albicans is a commensal organism and opportunistic pathogen associated both with superficial (mucosal and cutaneous) and systemic infections. Extensive use of antifungal agents has led to reduced susceptibility to the few existing drugs, which has encouraged the search for novel antifungal agents. Therefore, the present study investigated the antifungal activity of 2,6-bis[(E)-(4-pyridyl)methylidene]cyclohexanone (PMC) against C. albicans. METHODS: The in vitro activity of PMC was evaluated against C. albicans. Additionally, an invertebrate infection model in Caenorhabditis elegans as well as two infected murine models of oral and systemic candidiasis were used to determine the antifungal efficacy of PMC in vivo. RESULTS: Minimum inhibitory concentrations (MICs) of PMC ranged from 4-32μg/mL against nine clinical and two reference C. albicans isolates. Interestingly, PMC inhibited filamentation in vitro at subinhibitory concentrations similar to fluconazole. PMC also showed low toxicity against murine macrophages and human erythrocytes. In the invertebrate infection model, PMC was efficient in prolonging survival of C. elegans infected with C. albicans SC5314. Treatment with PMC was efficient both in murine models of systemic and oral candidiasis and was similar to that observed with conventional drug treatments (nystatin and fluconazole). CONCLUSIONS: The results of this study indicate the therapeutic potential of PMC as it was able to inhibit filamentation of C. albicans in vitro. These alterations to the fungi by PMC resulted in a reduction of oral and systemic infection in mice. In conclusion, we present promising evidence of the anticandidal activity of PMC in vitro and in vivo.
OBJECTIVES:Candida albicans is a commensal organism and opportunistic pathogen associated both with superficial (mucosal and cutaneous) and systemic infections. Extensive use of antifungal agents has led to reduced susceptibility to the few existing drugs, which has encouraged the search for novel antifungal agents. Therefore, the present study investigated the antifungal activity of 2,6-bis[(E)-(4-pyridyl)methylidene]cyclohexanone (PMC) against C. albicans. METHODS: The in vitro activity of PMC was evaluated against C. albicans. Additionally, an invertebrate infection model in Caenorhabditis elegans as well as two infected murine models of oral and systemic candidiasis were used to determine the antifungal efficacy of PMC in vivo. RESULTS: Minimum inhibitory concentrations (MICs) of PMC ranged from 4-32μg/mL against nine clinical and two reference C. albicans isolates. Interestingly, PMC inhibited filamentation in vitro at subinhibitory concentrations similar to fluconazole. PMC also showed low toxicity against murine macrophages and human erythrocytes. In the invertebrate infection model, PMC was efficient in prolonging survival of C. elegans infected with C. albicans SC5314. Treatment with PMC was efficient both in murine models of systemic and oral candidiasis and was similar to that observed with conventional drug treatments (nystatin and fluconazole). CONCLUSIONS: The results of this study indicate the therapeutic potential of PMC as it was able to inhibit filamentation of C. albicans in vitro. These alterations to the fungi by PMC resulted in a reduction of oral and systemic infection in mice. In conclusion, we present promising evidence of the anticandidal activity of PMC in vitro and in vivo.
Authors: Danielle da Nóbrega Alves; Alana Rodrigues Ferreira; Allana Brunna Sucupira Duarte; Ana Karoline Vieira Melo; Damião Pergentino de Sousa; Ricardo Dias de Castro Journal: Biomed Res Int Date: 2021-04-06 Impact factor: 3.411