| Autor: |
Lima-Neto RG; Laboratory for Research & Diagnosis in Tropical Diseases, Department of Tropical Medicine, Center for Medical Sciences, Federal University of Pernambuco (UFPE), Avenida Prof Moraes Rego s/n, Recife, Pernambuco, 50670-901, Brazil., Neta MS; Nantes Université, Cibles et médicaments des infections et de l'immunité, IICiMed, UR 1155, F-44000 Nantes, France.; Department of Pharmaceutical Sciences, Center for Health Sciences, UFPE, Brazil., Valeriano CA; Laboratory for Research & Diagnosis in Tropical Diseases, Department of Tropical Medicine, Center for Medical Sciences, Federal University of Pernambuco (UFPE), Avenida Prof Moraes Rego s/n, Recife, Pernambuco, 50670-901, Brazil., Neves RP; Departament of Mycology, Center for Biosciences, UFPE, Brazil., Lacerda AM; Departament of Mycology, Center for Biosciences, UFPE, Brazil., Ferraz CE; Laboratory for Research & Diagnosis in Tropical Diseases, Department of Tropical Medicine, Center for Medical Sciences, Federal University of Pernambuco (UFPE), Avenida Prof Moraes Rego s/n, Recife, Pernambuco, 50670-901, Brazil., Inácio CP; Departament of Mycology, Center for Biosciences, UFPE, Brazil., Le Pape P; Nantes Université, Cibles et médicaments des infections et de l'immunité, IICiMed, UR 1155, F-44000 Nantes, France., Ourliac-Garnier I; Nantes Université, Cibles et médicaments des infections et de l'immunité, IICiMed, UR 1155, F-44000 Nantes, France., Faria AR; Department of Pharmaceutical Sciences, Center for Health Sciences, UFPE, Brazil., Silva TG; Department of Antibiotics, Center for Biosciences, UFPE, Brazil., Pereira VR; Aggeu Magalhães Institute, Oswaldo Cruz Fundation, Recife, PE, 50740-465, Brazil., Marchand P; Nantes Université, Cibles et médicaments des infections et de l'immunité, IICiMed, UR 1155, F-44000 Nantes, France. |
| Abstrakt: |
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. |
