Covalent Conjugation Strategies for Antifungal Agents: Synthetic Approaches and Therapeutic Potential.

The increasing prevalence of invasive fungal infections, alongside rising resistance to conventional antifungal therapies, necessitates the development of improved treatment strategies. This review provides a comprehensive overview of recent advances in the design, synthesis, and biological evaluation of antifungal drug conjugates. Particular emphasis is placed on structural modifications of clinically used antifungal agents-such as azoles, echinocandins, and polyene macrolides-as well as novel conjugates incorporating coumarins, steroids, amino acids, and peptides. Conjugation strategies, including covalent attachment to small molecules, polymers, or bioactive moieties, have been employed to improve pharmacokinetic properties, reduce toxicity, and overcome drug resistance. The synthesis methods and biological profiles of selected conjugates are critically discussed, highlighting their potential as candidates for next-generation antifungal therapeutics. This review underscores the versatility of conjugation chemistry as a promising platform for antifungal drug development.