Anti-Sporothrix brasiliensis activity of different pyrazinoic acid prodrugs: a repurposing evaluation
Braz. J. Pharm. Sci. (Online)
;
54(4): e17858, 2018. tab, graf
Article
in English
| LILACS
| ID: biblio-1001585
ABSTRACT
From drug repurposing studies, this work aimed to evaluate the activity of different pyrazinoic acid (POA) derivatives against Sporothrix brasiliensis. The POA esters were prepared and characterized as previously reported by classical esterification reactions, with good to excellent yields. Sporothrix brasiliensis isolates from cats (n=6) and standard strains of S. brasiliensis and S. schenckii were used to assess the antifungal activity of the POA derivatives through broth microdilution assay (CLSI M38-A2). Among the tested compounds, molecules 3 and 4 showed fungistatic and fungicidal activities against all Sporothrix spp. strains, and the obtained MIC and MFC values ranged from 2.12 to 4.24 mg/mL and from 1.29 to 5.15 mg/mL, respectively. Compound 2 and 5 were active as in vitro inhibitors of fungal growth, but showed weak fungicidal activity, while molecules 1 and POA itself were inactive. The results suggest the activity of POA derivatives against Sporothrix spp. may be dependent on the lipophilicity. In addition, the antifungal susceptibility of the isolates to itraconazole was performed, showing that two Sporothrix isolates from cats were itraconazole-resistant. Compounds 3 and 4 were also active against these itraconazole-resistant isolates, indicating a possible alternative route to the standard mode of action of itraconazole.
Full text:
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Index:
LILACS (Americas)
Main subject:
Sporotrichosis
/
Sporothrix
/
Prodrugs
/
Itraconazole
Limits:
Animals
Country/Region as subject:
South America
/
Brazil
Language:
English
Journal:
Braz. J. Pharm. Sci. (Online)
Journal subject:
Farmacologia
/
Teraputica
/
Toxicologia
Year:
2018
Type:
Article
Affiliation country:
Brazil
Institution/Affiliation country:
Universidade Federal de Pelotas/BR
/
Universidade Federal de São Paulo/BR
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