Proteomic identification of metabolic changes in Paracoccidioides brasiliensisinduced by a nitroheteroarylchalcone

Aim:To access the metabolic changes caused by a chalcone derivative (LabMol-75) through a proteomic approach. Methods:Proteomic analysis was performed after 9 h of Paracoccidioides brasiliensisyeast (Pb18) cell incubation with the LabMol-75at MIC. The proteomic findings were validated through in vitroand in silicoassays. Results:Exposure to the compound led to the downregulation of proteins associated with glycolysis and gluconeogenesis, β-oxidation, the citrate cycle and the electron transport chain. Conclusion:LabMol-75caused an energetic imbalance in the fungus metabolism and deep oxidative stress. Additionally, the in silicomolecular docking approach pointed to this molecule as a putative competitive inhibitor of DHPS.