Repurposing Benzimidazoles against Causative Agents of Chromoblastomycosis: Albendazole Has Superior In Vitro Activity Than Mebendazole and Thiabendazole
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 repositio...
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| Format: | Article |
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MDPI AG
2023-07-01
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| Series: | Journal of Fungi |
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| Online Access: | https://www.mdpi.com/2309-608X/9/7/753 |
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| author | Rowena Alves Coelho Maria Helena Galdino Figueiredo-Carvalho Fernando Almeida-Silva Vanessa Brito de Souza Rabello Gabriela Rodrigues de Souza Leandro Stefano Sangenito Luna Sobrino Joffe André Luis Souza dos Santos Maria Cristina da Silva Lourenço Marcio L. Rodrigues Rodrigo Almeida-Paes |
| author_facet | Rowena Alves Coelho Maria Helena Galdino Figueiredo-Carvalho Fernando Almeida-Silva Vanessa Brito de Souza Rabello Gabriela Rodrigues de Souza Leandro Stefano Sangenito Luna Sobrino Joffe André Luis Souza dos Santos Maria Cristina da Silva Lourenço Marcio L. Rodrigues Rodrigo Almeida-Paes |
| author_sort | Rowena Alves Coelho |
| collection | DOAJ |
| description | 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 <i>Fonsecaea pedrosoi</i>. 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. |
| first_indexed | 2024-03-11T00:55:43Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2309-608X |
| language | English |
| last_indexed | 2024-03-11T00:55:43Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Fungi |
| spelling | doaj.art-6a359483e7f245af8aaa8bc78a918ebf2023-11-18T20:01:56ZengMDPI AGJournal of Fungi2309-608X2023-07-019775310.3390/jof9070753Repurposing Benzimidazoles against Causative Agents of Chromoblastomycosis: Albendazole Has Superior In Vitro Activity Than Mebendazole and ThiabendazoleRowena Alves Coelho0Maria Helena Galdino Figueiredo-Carvalho1Fernando Almeida-Silva2Vanessa Brito de Souza Rabello3Gabriela Rodrigues de Souza4Leandro Stefano Sangenito5Luna Sobrino Joffe6André Luis Souza dos Santos7Maria Cristina da Silva Lourenço8Marcio L. Rodrigues9Rodrigo Almeida-Paes10Laboratório de Micologia, Instituto Nacional de Infectologia Evandro Chagas, INI/Fiocruz, Rio de Janeiro 21040-900, RJ, BrazilLaboratório de Micologia, Instituto Nacional de Infectologia Evandro Chagas, INI/Fiocruz, Rio de Janeiro 21040-900, RJ, BrazilLaboratório de Micologia, Instituto Nacional de Infectologia Evandro Chagas, INI/Fiocruz, Rio de Janeiro 21040-900, RJ, BrazilLaboratório de Micologia, Instituto Nacional de Infectologia Evandro Chagas, INI/Fiocruz, Rio de Janeiro 21040-900, RJ, BrazilPlataforma de Bioensaios RPT 11B, Instituto Nacional de Infectologia Evandro Chagas, INI/Fiocruz, Rio de Janeiro 21040-900, RJ, BrazilLaboratório 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, BrazilDepartment of Microbiology and Immunology, Stony Brook University, Stony Brook, NY 11792, USALaboratório 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, BrazilPlataforma de Bioensaios RPT 11B, Instituto Nacional de Infectologia Evandro Chagas, INI/Fiocruz, Rio de Janeiro 21040-900, RJ, BrazilInstituto Carlos Chagas, Fundação Oswaldo Cruz, Curitiba 81350-010, PR, BrazilLaboratório de Micologia, Instituto Nacional de Infectologia Evandro Chagas, INI/Fiocruz, Rio de Janeiro 21040-900, RJ, BrazilChromoblastomycosis (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 <i>Fonsecaea pedrosoi</i>. 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.https://www.mdpi.com/2309-608X/9/7/753chromoblastomycosis<i>Fonsecaea pedrosoi</i>drug repositioningbenzimidazolesalbendazole |
| spellingShingle | Rowena Alves Coelho Maria Helena Galdino Figueiredo-Carvalho Fernando Almeida-Silva Vanessa Brito de Souza Rabello Gabriela Rodrigues de Souza Leandro Stefano Sangenito Luna Sobrino Joffe André Luis Souza dos Santos Maria Cristina da Silva Lourenço Marcio L. Rodrigues Rodrigo Almeida-Paes Repurposing Benzimidazoles against Causative Agents of Chromoblastomycosis: Albendazole Has Superior In Vitro Activity Than Mebendazole and Thiabendazole Journal of Fungi chromoblastomycosis <i>Fonsecaea pedrosoi</i> drug repositioning benzimidazoles albendazole |
| title | Repurposing Benzimidazoles against Causative Agents of Chromoblastomycosis: Albendazole Has Superior In Vitro Activity Than Mebendazole and Thiabendazole |
| title_full | Repurposing Benzimidazoles against Causative Agents of Chromoblastomycosis: Albendazole Has Superior In Vitro Activity Than Mebendazole and Thiabendazole |
| title_fullStr | Repurposing Benzimidazoles against Causative Agents of Chromoblastomycosis: Albendazole Has Superior In Vitro Activity Than Mebendazole and Thiabendazole |
| title_full_unstemmed | Repurposing Benzimidazoles against Causative Agents of Chromoblastomycosis: Albendazole Has Superior In Vitro Activity Than Mebendazole and Thiabendazole |
| title_short | Repurposing Benzimidazoles against Causative Agents of Chromoblastomycosis: Albendazole Has Superior In Vitro Activity Than Mebendazole and Thiabendazole |
| title_sort | repurposing benzimidazoles against causative agents of chromoblastomycosis albendazole has superior in vitro activity than mebendazole and thiabendazole |
| topic | chromoblastomycosis <i>Fonsecaea pedrosoi</i> drug repositioning benzimidazoles albendazole |
| url | https://www.mdpi.com/2309-608X/9/7/753 |
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