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Synthetic Derivatives against Wild-Type and Non-Wild-Type Sporothrix brasiliensis: In Vitro and In Silico Analyses
Recently, the well-known geographically wide distribution of sporotrichosis in Brazil, combined with the difficulties of effective domestic feline treatment, has emphasized the pressing need for new therapeutic alternatives. This work considers a range of synthetic derivatives as potential antifunga...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8781075/ https://www.ncbi.nlm.nih.gov/pubmed/35056112 http://dx.doi.org/10.3390/ph15010055 |
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author | de Souza, Lais Cavalcanti dos Santos Velasco Alcântara, Lucas Martins de Macêdo-Sales, Pãmella Antunes Reis, Nathália Faria de Oliveira, Débora Sena Machado, Ricardo Luiz Dantas Geraldo, Reinaldo Barros dos Santos, André Luis Souza Ferreira, Vítor Francisco Gonzaga, Daniel Tadeu Gomes da Silva, Fernando de Carvalho Castro, Helena Carla Baptista, Andréa Regina de Souza |
author_facet | de Souza, Lais Cavalcanti dos Santos Velasco Alcântara, Lucas Martins de Macêdo-Sales, Pãmella Antunes Reis, Nathália Faria de Oliveira, Débora Sena Machado, Ricardo Luiz Dantas Geraldo, Reinaldo Barros dos Santos, André Luis Souza Ferreira, Vítor Francisco Gonzaga, Daniel Tadeu Gomes da Silva, Fernando de Carvalho Castro, Helena Carla Baptista, Andréa Regina de Souza |
author_sort | de Souza, Lais Cavalcanti dos Santos Velasco |
collection | PubMed |
description | Recently, the well-known geographically wide distribution of sporotrichosis in Brazil, combined with the difficulties of effective domestic feline treatment, has emphasized the pressing need for new therapeutic alternatives. This work considers a range of synthetic derivatives as potential antifungals against Sporothrix brasiliensis isolated from cats from the hyperendemic Brazilian region. Six S. brasiliensis isolates from the sporotrichotic lesions of itraconazole responsive or non-responsive domestic cats were studied. The minimum inhibitory concentrations (MICs) of three novel hydrazone derivatives and eleven novel quinone derivatives were determined using the broth microdilution method (M38-A2). In silico tests were also used to predict the pharmacological profile and toxicity parameters of these synthetic derivatives. MICs and MFCs ranged from 1 to >128 µg/mL. The ADMET computational analysis failed to detect toxicity while a good pharmacological predictive profile, with parameters similar to itraconazole, was obtained. Three hydrazone derivatives were particularly promising candidates as antifungal agents against itraconazole-resistant S. brasiliensis from the Brazilian hyperendemic region. Since sporotrichosis is a neglected zoonosis currently spreading in Latin America, particularly in Brazil, the present data can contribute to its future control by alternative antifungal drug design against S. brasiliensis, the most virulent and prevalent species of the hyperendemic context. |
format | Online Article Text |
id | pubmed-8781075 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87810752022-01-22 Synthetic Derivatives against Wild-Type and Non-Wild-Type Sporothrix brasiliensis: In Vitro and In Silico Analyses de Souza, Lais Cavalcanti dos Santos Velasco Alcântara, Lucas Martins de Macêdo-Sales, Pãmella Antunes Reis, Nathália Faria de Oliveira, Débora Sena Machado, Ricardo Luiz Dantas Geraldo, Reinaldo Barros dos Santos, André Luis Souza Ferreira, Vítor Francisco Gonzaga, Daniel Tadeu Gomes da Silva, Fernando de Carvalho Castro, Helena Carla Baptista, Andréa Regina de Souza Pharmaceuticals (Basel) Article Recently, the well-known geographically wide distribution of sporotrichosis in Brazil, combined with the difficulties of effective domestic feline treatment, has emphasized the pressing need for new therapeutic alternatives. This work considers a range of synthetic derivatives as potential antifungals against Sporothrix brasiliensis isolated from cats from the hyperendemic Brazilian region. Six S. brasiliensis isolates from the sporotrichotic lesions of itraconazole responsive or non-responsive domestic cats were studied. The minimum inhibitory concentrations (MICs) of three novel hydrazone derivatives and eleven novel quinone derivatives were determined using the broth microdilution method (M38-A2). In silico tests were also used to predict the pharmacological profile and toxicity parameters of these synthetic derivatives. MICs and MFCs ranged from 1 to >128 µg/mL. The ADMET computational analysis failed to detect toxicity while a good pharmacological predictive profile, with parameters similar to itraconazole, was obtained. Three hydrazone derivatives were particularly promising candidates as antifungal agents against itraconazole-resistant S. brasiliensis from the Brazilian hyperendemic region. Since sporotrichosis is a neglected zoonosis currently spreading in Latin America, particularly in Brazil, the present data can contribute to its future control by alternative antifungal drug design against S. brasiliensis, the most virulent and prevalent species of the hyperendemic context. MDPI 2022-01-01 /pmc/articles/PMC8781075/ /pubmed/35056112 http://dx.doi.org/10.3390/ph15010055 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article de Souza, Lais Cavalcanti dos Santos Velasco Alcântara, Lucas Martins de Macêdo-Sales, Pãmella Antunes Reis, Nathália Faria de Oliveira, Débora Sena Machado, Ricardo Luiz Dantas Geraldo, Reinaldo Barros dos Santos, André Luis Souza Ferreira, Vítor Francisco Gonzaga, Daniel Tadeu Gomes da Silva, Fernando de Carvalho Castro, Helena Carla Baptista, Andréa Regina de Souza Synthetic Derivatives against Wild-Type and Non-Wild-Type Sporothrix brasiliensis: In Vitro and In Silico Analyses |
title | Synthetic Derivatives against Wild-Type and Non-Wild-Type Sporothrix brasiliensis: In Vitro and In Silico Analyses |
title_full | Synthetic Derivatives against Wild-Type and Non-Wild-Type Sporothrix brasiliensis: In Vitro and In Silico Analyses |
title_fullStr | Synthetic Derivatives against Wild-Type and Non-Wild-Type Sporothrix brasiliensis: In Vitro and In Silico Analyses |
title_full_unstemmed | Synthetic Derivatives against Wild-Type and Non-Wild-Type Sporothrix brasiliensis: In Vitro and In Silico Analyses |
title_short | Synthetic Derivatives against Wild-Type and Non-Wild-Type Sporothrix brasiliensis: In Vitro and In Silico Analyses |
title_sort | synthetic derivatives against wild-type and non-wild-type sporothrix brasiliensis: in vitro and in silico analyses |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8781075/ https://www.ncbi.nlm.nih.gov/pubmed/35056112 http://dx.doi.org/10.3390/ph15010055 |
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