Argentilactone molecular targets in Paracoccidioides brasiliensis identified by chemoproteomics

The etiological agents of PCM belong to the Paracoccidioides genus, which is restricted to Latin America. The infection is acquired through inhalation of conidia that primarily lodge in the lungs and may disseminate to other organs/tissues. Treatment of PCM is commonly achieved via administration of antifungals of the azole class, sulfonamides, and amphotericin B. The antifungal toxicity and side effects, added to the long treatment time has driven research for new bioactive compounds. Argentilactone, compound isolated from a Brazilian savanna plant Hyptis ovaliofolia, has been suggested as potent antifungal, inhibiting dimorphism of P. brasiliensis and the enzymatic activity of isocitrate lyase, a key enzyme of the glyoxylate cycle. Furthermore, it has no cytotoxicity and genotoxicity in fibroblast cells at concentrations that inhibit the fungal growth. This work was developed due to the importance of elucidating the putative mode of action of argentilactone. The chemoproteomics approach, by affinity chromatography, was the methodology used to explore the interactions between P. brasiliensis proteins and argentilactone