The increasing prevalence of fungal infections and the growing resistance to existing antifungal agents underscore the urgent need for new therapeutic alternatives. Curcumin has demonstrated antifungal potential; however, its poor solubility and bioavailability limit its clinical application. To address these challenges, this thesis explored the antifungal activity of curcumin analogs.
This research of Veridianna Camilo Pattini identified potent antifungal compounds, particularly 3,3’-dimethoxycurcumin (DMC), which exhibited strong activity against Candida and dermatophyte species and demonstrated a synergistic effect when combined with terbinafine. DMC specifically targeted the membranes of Candida species by forming a complex with ergosterol and showed no toxicity in the Galleria mellonella in vivo model.
Additionally, 3-hydroxy-dibenzylideneacetone displayed potent antifungal activity, outperforming fluconazole against certain Candida species. It effectively inhibited fungal adhesion and biofilm formation while exhibiting synergy with other antifungal agents. The compound targeted both the fungal membrane and cell wall, demonstrating improved stability and lower toxicity compared to curcumin.
To explore potential biomedical applications of curcumin analogs, a 2-hydroxy-dibenzylideneacetone coating was tested for its antifouling properties against Candida biofilms. The coating significantly reduced fungal adhesion, hyphal growth, and biofilm formation while downregulating key biofilm-related genes. These findings support its potential use as an antifouling coating for preventing Candida-associated infections.
Overall, this research provides valuable insights into the structure-activity relationships of curcuminoids, contributing to the development of novel antifungal agents and biofilm-preventing coatings.