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2. Antifungal efficacy of imidazo[1,2-a]pyrazine-based thiosemicarbazones and thiazolidinediones against Sporothrix species

Author

Neto, Reginaldo GL, primary, Neta, Marlene SA, additional, Valeriano, Carlos AT, additional, Neves, Rejane P, additional, Lacerda, Armando M, additional, Ferraz, Claudia E, additional, Inácio, Cícero P, additional, Pape, Patrice, additional, Ourliac-Garnier, Isabelle, additional, Faria, Antônio R, additional, Silva, Teresinha G, additional, Pereira, Valéria RA, additional, and Marchand, Pascal, additional

Published
2023
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3. Antifungal efficacy of imidazo[1,2-a]pyrazine-based thiosemicarbazones and thiazolidinediones against Sporothrixspecies

Author

Lima-Neto, Reginaldo G, Neta, Marlene SA, Valeriano, Carlos AT, Neves, Rejane P, Lacerda, Armando M, Ferraz, Claudia E, Inácio, Cícero P, Le Pape, Patrice, Ourliac-Garnier, Isabelle, Faria, Antônio R, Silva, Teresinha G, Pereira, Valéria RA, and Marchand, Pascal

Abstract

Aim:To evaluate antifungal potential of 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine hybrids based on thiosemicarbazones and thiazolidinediones against pathogenic Sporothrixspecies. Methods:Antifungal activity of nine compounds were assessed by broth microdilution. Interactions between active compounds and itraconazole were evaluated by the checkerboard assay using non-wild-type isolates. Cytotoxicity of the compounds was determined. Results:Four C-3 substituted analogs showed antifungal activity, unrelated to thiosemicarbazone or thiazolidinedione functions. Synergistic interactions between the four compounds and itraconazole, and low toxicity on mouse fibroblast cells were observed. Activity of 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine hybrids against Sporothrixdepended on the substitution on the imidazopyrazine ring. Conclusion:Antifungal potential, overcoming itraconazole resistance and low toxicity indicate the possible use of that series of compounds in a therapeutic alternative for treatment of sporotrichosis.

Published
2023
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4. Antifungal efficacy of imidazo[1,2- a ]pyrazine-based thiosemicarbazones and thiazolidinediones against Sporothrix species.

Author

Lima-Neto RG, Neta MS, Valeriano CA, Neves RP, Lacerda AM, Ferraz CE, Inácio CP, Le Pape P, Ourliac-Garnier I, Faria AR, Silva TG, Pereira VR, and Marchand P

Subjects
Animals, Mice, Antifungal Agents pharmacology, Itraconazole pharmacology, Microbial Sensitivity Tests, Sporothrix, Thiosemicarbazones pharmacology, Thiazolidinediones
Abstract

Aim: To evaluate antifungal potential of 5,6,7,8-tetrahydroimidazo[1,2- a ]pyrazine hybrids based on thiosemicarbazones and thiazolidinediones against pathogenic Sporothrix species. Methods: Antifungal activity of nine compounds were assessed by broth microdilution. Interactions between active compounds and itraconazole were evaluated by the checkerboard assay using non-wild-type isolates. Cytotoxicity of the compounds was determined. Results: Four C-3 substituted analogs showed antifungal activity, unrelated to thiosemicarbazone or thiazolidinedione functions. Synergistic interactions between the four compounds and itraconazole, and low toxicity on mouse fibroblast cells were observed. Activity of 5,6,7,8-tetrahydroimidazo[1,2- a ]pyrazine hybrids against Sporothrix depended on the substitution on the imidazopyrazine ring. Conclusion: Antifungal potential, overcoming itraconazole resistance and low toxicity indicate the possible use of that series of compounds in a therapeutic alternative for treatment of sporotrichosis.

Published
2023
Full Text
View/download PDF

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