Synthetic Sinapates: Antifungal, Molecular Docking, and ADMET Studies

The increasing incidence of diseases resulting from fungal infections is due to the high morbidity and mortality associated with these microorganisms. Sinapic acid is a plant-derived phenolic compound with antifungal activity. Therefore, in this study, a collection of eleven sinapates (1-11) was prepared and the antifungal activity of these compounds was evaluated against Candida albicans and Candida tropicalis. Compounds 4, 5, and 8 showed good antifungal activity. Compound 4 presented minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values of 62.5 µg/mL against C. albicans and 15.62 µg/mL against C. tropicalis. Compound 5 showed MIC and MFC values of 7.81 µg/mL against both strains, while compound 8 presented MIC and MFC values of 15.62 µg/mL against C. albicans and 62.5 µg/mL against C. tropicalis. The ratio MFC/MIC<4 showed that the compounds exerted a fungicidal effect. The ergosterol assay suggests that the mechanism of action occurs via the plasma membrane. The silico study, including ADMET predictions, suggested that most of the compounds have satisfactory pharmacokinetic and toxicological properties. Therefore, sinapates appear to be promising prototypes for the development of new anti-Candida drug candidates.