Repurposing Benzimidazoles against Causative Agents of Chromoblastomycosis: Albendazole Has Superior In Vitro Activity Than Mebendazole and Thiabendazole

Author:

Coelho Rowena Alves1ORCID,Figueiredo-Carvalho Maria Helena Galdino1,Almeida-Silva Fernando1ORCID,de Souza Rabello Vanessa Brito1,de Souza Gabriela Rodrigues2,Sangenito Leandro Stefano34,Joffe Luna Sobrino5,Santos André Luis Souza dos36ORCID,da Silva Lourenço Maria Cristina2,Rodrigues Marcio L.78ORCID,Almeida-Paes Rodrigo16ORCID

Affiliation:

1. Laboratório de Micologia, Instituto Nacional de Infectologia Evandro Chagas, INI/Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil

2. Plataforma de Bioensaios RPT 11B, Instituto Nacional de Infectologia Evandro Chagas, INI/Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil

3. Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes, Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Goés, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil

4. Instituto Federal de Educação, Ciência e Tecnologia do Rio de Janeiro, Nilópolis 26530-060, RJ, Brazil

5. Department of Microbiology and Immunology, Stony Brook University, Stony Brook, NY 11792, USA

6. Rede Micologia RJ, Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Rio de Janeiro 21941-901, RJ, Brazil

7. Instituto Carlos Chagas, Fundação Oswaldo Cruz, Curitiba 81350-010, PR, Brazil

8. Instituto de Microbiologia, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, RJ, Brazil

Abstract

Chromoblastomycosis (CBM) is a neglected human implantation mycosis caused by several dematiaceous fungal species. Currently available therapy is usually associated with physical methods, especially surgery, and with high refractoriness. Therefore, drug discovery for CBM is essential. Drug repositioning is a strategy used to facilitate the discovery of new treatments for several diseases. The aim of this study was to discover substances with antifungal activity against CBM agents from a collection of drugs previously approved for use in human diseases. A screening was performed with the NIH Clinical Collection against Fonsecaea pedrosoi. Ten substances, with clinical applicability in CBM, inhibited fungal growth by at least 60%. The minimum inhibitory concentration (MIC) of these substances was determined against other CBM agents, and the benzimidazoles albendazole, mebendazole and thiabendazole presented the lowest MIC values. The selectivity index, based on MIC and cytotoxicity of these substances, revealed albendazole to be more selective. To investigate a possible synergism of this benzimidazole with itraconazole and terbinafine, the chequerboard method was used. All interactions were classified as indifferent. Our current results suggest that benzimidazoles have repositioning potential against CBM agents. Albendazole seems to be the most promising, since it presented the highest selectivity against all dematiaceous fungi tested.

Funder

Programa Inova Fiocruz

Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro

Publisher

MDPI AG

Subject

Plant Science,Ecology, Evolution, Behavior and Systematics,Microbiology (medical)

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