Synthesis, In Vitro and In Vivo Antifungal Activities of Novel Coumarin–Tryptophan Conjugates

Objective: Persistent fungal infections, especially those caused by Candida spp., pose a serious health risk to humans. Treatment of these infections is highly challenging due to the spread of resistance to first-line antifungal drugs. Therefore, the identification and development of novel antifungal agents are in great demand. In this study, a series of coumarin–tryptophan conjugates were synthesized and their antifungal activities evaluated. Methods: In vitro antifungal activities of compounds (IVa–IVe) were determined by the minimum inhibitory concentration (MIC) method. The in vivo activity of the most active compound, (IVe), was assessed using a murine model of dermal candidiasis. Docking studies were performed using the AutoDock 4.0 software package. Results and Discussion: Several compounds exhibited broad-spectrum activity against the tested strains, with favorable MIC values in the range of 6.25–25 µg/mL. Compound (IVe) showed significant antifungal activity with an MIC of 6.25 µg/mL against A. flavus and C. albicans. In the murine dermal candidiasis model, (IVe) reduced the fungal burden in nearly all vital organs of the experimental animals and demonstrated therapeutic healing effects on ulcers induced by C. albicans infection. Molecular docking results indicated that these compounds have potential as antifungal agents. Evaluation of drug-like properties of compounds (IVa–IVe) using the SwissADME web tool revealed that these molecules possess favorable druggability profiles. Conclusions: Compound (IVe), having shown excellent antifungal activity, can be considered a promising antifungal agent for further investigation.