Benzylidene-carbonyl compounds are active against itraconazole-susceptible and itraconazole-resistant Sporothrix brasiliensis

We evaluated the antifungal activity of benzylidene-carbonyl compounds (LINS03) based on the structure of gibbilimbol from Piper malacophyllum Linn. Five analogues ( 1 – 5 ) were synthetized following a classic aldol condensation between an aromatic aldehyde and a ketone, under basic conditions. These were tested against itraconazole-susceptible ( n = 3) and itraconazole-resistant ( n = 5) isolates of Sporothrix brasiliensis by M38-A2 guidelines of CLSI. All of them were fungistatic (MIC ranged of 0.11–0.22 mg/mL ( 1 ); 0.08–0.17 mg/mL ( 2 ); 0.05–0.1 mg/mL ( 3 ); 0.04–0.33 mg/mL ( 4 ); and 0.04–0.3 mg/mL ( 5 )), highlighting compounds 2 and 3 . As fungicidal, compounds 1 and 2 were highlighted (MFC ranged of 0.22–0.89 mg/mL and 0.08–1.35 mg/mL, respectively), compared with the remaining (0.77–> 3.08 mg/mL ( 3 ); 0.08–> 2.6 mg/mL ( 4 ); and 0.59–> 2.37 mg/mL ( 5 )). The inhibitory activity was related to the benzylidene-carbonyl, whereas the phenol group and the low chain homolog seems to contribute to some extent to the fungicidal effect. Compound 2 highlighted due to the considerable fungistatic and fungicidal activities, including itraconazole-resistant Sporothrix brasiliensis . These findings support the potential usefulness of benzylidene-carbonyl compounds as promising prototypes for the development of antifungal against sporotrichosis by Sporothrix brasiliensis , including against itraconazole-resistant isolates.