Pyridoxal and Salicylaldehyde Derivatives: Synthesis, Characterization, and Antifungal Potential Against Opportunistic Yeast Pathogens

This study reports the synthesis, characterization, and antifungal evaluation of a series of pyridoxal and salicylaldehyde derivatives, using synthetic methodologies such as radical cyclizations and click chemistry. Compounds <b>6a</b> and <b>6b</b>, featuring a fused dihydrobenzoxepine-pyridine scaffold, demonstrated effective fungicidal activity with MIC values of 19 µg/mL against <i>Cryptococcus neoformans</i> 2807. Similarly, compound <b>6b</b> exhibited notable activity with a MIC of 75 µg/mL against <i>Candida auris</i> PUJ-HUSI 537. Both compounds outperformed fluconazole (FLC) in these strains. In silico ADMET profiling revealed favorable pharmacokinetic properties, including blood-brain barrier penetration and drug-likeness parameters consistent with Lipinski's rule of five. Cytotoxicity assays on human fibroblasts confirmed the low toxicity of compound <b>6a</b> at the tested concentrations. These results highlight the potential of the fused dihydrobenzoxepine-pyridine scaffold as a promising antifungal candidate for further investigations.