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.

Abstract In the typical activities of quarries, it is common for the employees to be exposed to diverse risk factors, pertaining to their health or physical integrity. This kind of exposition, in Brazil, entitles these employees to additional payments, defined in law from different technical parameters. The controversies concerning the payment of these premiums between the employers and the employees, like the other conflicts between capital and labor, are solved in Brazil by the Labor Courts, and the forensic expert survey is one of the main tools used by the judges. This study aimed to characterize the unhealthy or hazardous situations in quarries using the forensic expert survey, focusing on the concepts and the legal definitions of the unhealthy or hazardous situations in labor activities, as well as the main aspects of the expert evidence technique and the judicial proceeding. This analysis revealed that most of the functions in quarries mean exposure to hazards, requiring appropriate management