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J. Fungi 2018, 4(4), 134; https://doi.org/10.3390/jof4040134

Anti-Candida albicans Activity of Thiazolylhydrazone Derivatives in Invertebrate and Murine Models

1
Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Presidente Antônio Carlos, 6627, Pampulha, Belo Horizonte—Minas Gerais 31270-901, Brasil
2
Departamento de Biociências e Diagnóstico Bucal, Instituto de Ciência e Tecnologia de São José dos Campos—UNESP, Av. Francisco José Longe, 777, Jardim São Dimas, São José dos Campos—São Paulo 12245-000, Brasil
3
Department of Molecular Genetics and Microbiology, Division of Infectious Diseases, Stony Brook University, 150 Life Science Building, Stony Brook, NY 11794, USA
4
Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte—Minas Gerais 31270-901, Brasil
5
Division of Infectious Diseases, Rhode Island Hospital, Alpert Medical School, and Brown University, Providence, RI 02903, USA
*
Author to whom correspondence should be addressed.
Received: 16 October 2018 / Revised: 5 December 2018 / Accepted: 10 December 2018 / Published: 12 December 2018
(This article belongs to the Special Issue Alternative Models for the Study of Fungal Host-Pathogen Interactions)
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Abstract

Candidiasis is an opportunistic fungal infection with Candida albicans being the most frequently isolated species. Treatment of these infections is challenging due to resistance that can develop during therapy, and the limited number of available antifungal compounds. Given this situation, the aim of this study was to evaluate the antifungal activity of four thiazolylhydrazone compounds against C. albicans. Thiazolylhydrazone compounds 1, 2, 3, and 4 were found to exert antifungal activity, with MICs of 0.125–16.0 μg/mL against C. albicans. The toxicity of the compounds was evaluated using human erythrocytes and yielded LC50 > 64 μg/mL. The compounds were further evaluated using the greater wax moth Galleria mellonella as an in vivo model. The compounds prolonged larval survival when tested between 5 and 15 mg/kg, performing as well as fluconazole. Compound 2 was evaluated in murine models of oral and systemic candidiasis. In the oral model, compound 2 reduced the fungal load on the mouse tongue; and in the systemic model it reduced the fungal burden found in the kidney when tested at 10 mg/kg. These results show that thiazolylhydrazones are an antifungal towards C. albicans with in vivo efficacy. View Full-Text
Keywords: Candida albicans; thiazolylhydrazone derivatives; antifungal Candida albicans; thiazolylhydrazone derivatives; antifungal
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Cruz, L.I.B.; Lopes, L.F.F.; De Camargo Ribeiro, F.; De Sá, N.P.; Lino, C.I.; Tharmalingam, N.; De Oliveira, R.B.; Rosa, C.A.; Mylonakis, E.; Fuchs, B.B.; Johann, S. Anti-Candida albicans Activity of Thiazolylhydrazone Derivatives in Invertebrate and Murine Models. J. Fungi 2018, 4, 134.

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