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Evaluation of 1,3-benzoxathiol-2-one Derivatives as Potential Antifungal Agents

[ Vol. 14 , Issue. 3 ]

Author(s):

Luciana Terra, Eliza de L. Chazin, Paola de S. Sanches, Max Saito, Marcus V.N. de Souza, Claudia R.B. Gomes, James L. Wardell, Solange M.S.V. Wardell, Plinio C. Sathler, Gabriela C.C. Silva, Viviane O. Lione, Marcos Kalil, Ana Joffily, Helena C. Castro* and Thatyana R.A. Vasconcelos*   Pages 304 - 310 ( 7 )

Abstract:


Background: Over the last few years, fungal infections have emerged as a worrisome global public health problem. Candidiasis is a disease caused by Candida species and has been a problem worldwide mainly for immunosuppressed patients. Lately, the resistant strains and side effects have been reported as important issues for treating Candidiasis, which have to be solved by identifying new drugs.

Objective: The goal of this work was to synthesize a series of 1,3-benzoxathiol-2-one derivatives, XYbenzo[ d][1,3]oxathiol-2-ones, and evaluate their antifungal activity against five Candida species.

Methods: In vitro antifungal screening test and minimum inhibitory concentration determination were performed according to CLSI protocols using ketoconazole as the reference drug. The cytotoxicity of the most active compounds was evaluated by hemolysis and MTT (Vero cells) assays.

Results: Compounds 2 (XY = 6-hydroxy-5-nitro, MIC = 4-32 µg/mL) and 7 (XY = 6-acetoxy-5-nitro, MIC =16-64 µg/mL) showed good results when compared with current antifungals in CLSI values (MIC = 0.04-250 µg/mL). These compounds exhibited a safer cytotoxicity as well as a lower hemolytic profile than ketoconazole.

Conclusion: Overall, the in vitro results pointed to the potential of compounds 2 and 7 as new antifungal prototypes to be further explored.

Keywords:

1, 3-Benzoxathiol-2-one, antifungal activity, crystallography, cytotoxic assays, Candida species, heterocycles.

Affiliation:

Programa de Pos-Graduacao em Ciencias e Biotecnologia, Instituto de Biologia, Universidade Federal Fluminense, Outeiro de Sao Joao Batista s/no, Centro, Niteroi, 24020-141, RJ, Programa de Pos-Graduacao em Quimica, Instituto de Quimica, Universidade Federal Fluminense, Outeiro de Sao Joao Batista s/no, Centro, Niteroi, 24020-141, RJ, Programa de Pos-Graduacao em Quimica, Instituto de Quimica, Universidade Federal Fluminense, Outeiro de Sao Joao Batista s/no, Centro, Niteroi, 24020-141, RJ, Programa de Pos-Graduacao em Patologia, Hospital Universitario Antonio Pedro, Universidade Federal Fluminense, Rua Marques do Parana 300, Centro, Niteroi, 24033-900, RJ, Instituto de Tecnologia em Farmacos – Farmanguinhos, Fundacao Oswaldo Cruz, Rua Sizenando Nabuco 100, Manguinhos, Rio de Janeiro, 21041-250, RJ, Instituto de Tecnologia em Farmacos – Farmanguinhos, Fundacao Oswaldo Cruz, Rua Sizenando Nabuco 100, Manguinhos, Rio de Janeiro, 21041-250, RJ, Instituto de Tecnologia em Farmacos – Farmanguinhos, Fundacao Oswaldo Cruz, Rua Sizenando Nabuco 100, Manguinhos, Rio de Janeiro, 21041-250, RJ, CHEMSOL, 1 Harcourt Road, Aberdeen AB15 5NY, Programa de Pos-Graduacao em Patologia, Hospital Universitario Antonio Pedro, Universidade Federal Fluminense, Rua Marques do Parana 300, Centro, Niteroi, 24033-900, RJ, Departamento de Farmacos e Medicamentos, Faculdade de Farmacia, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho 373, Cidade Universitaria, Rio de Janeiro, 21941- 902, RJ, Departamento de Farmacos e Medicamentos, Faculdade de Farmacia, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho 373, Cidade Universitaria, Rio de Janeiro, 21941- 902, RJ, Programa de Pos-Graduacao em Ciencias e Biotecnologia, Instituto de Biologia, Universidade Federal Fluminense, Outeiro de Sao Joao Batista s/no, Centro, Niteroi, 24020-141, RJ, Programa de Pos-Graduacao em Ciencias e Biotecnologia, Instituto de Biologia, Universidade Federal Fluminense, Outeiro de Sao Joao Batista s/no, Centro, Niteroi, 24020-141, RJ, Programa de Pos-Graduacao em Ciencias e Biotecnologia, Instituto de Biologia, Universidade Federal Fluminense, Outeiro de Sao Joao Batista s/no, Centro, Niteroi, 24020-141, RJ, Programa de Pos-Graduacao em Quimica, Instituto de Quimica, Universidade Federal Fluminense, Outeiro de Sao Joao Batista s/no, Centro, Niteroi, 24020-141, RJ

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