Nanoparticle antifungal agents: design, synthesis and docking studies of lactose thiourea derivatives

Fungal infections represent a growing global health crisis, with antifungal drug resistance emerging as a critical challenge. Developing structurally novel compounds offers a promising strategy to address resistance mechanisms. In this work, we report the design, synthesis, and biological evaluation of lactose-benzothiazole thiourea conjugates formulated as nanoparticles for enhanced antifungal delivery. The synthesized compounds exhibited promising antifungal activity against C. albicans, with compound 3k showing the most potent activity (MIC = 0.125 μg/mL), comparable to fluconazole. Selected compounds also demonstrated antibacterial activity against Staphylococcus epidermidis. Molecular docking studies revealed favorable binding interactions with C. albicans lanosterol 14α-demethylase (CYP51, PDB: 1EA1), with binding energies of − 6.8 to − 7.7 kcal/mol. To the best of our knowledge, this study presents the first report of lactose-benzothiazole thiourea conjugates as nanoparticle-based antifungal agents, demonstrating their potential to overcome drug resistance through alternative binding modes and enhanced cellular uptake, offering a promising scaffold for next-generation antifungal therapeutics.