Discovery of highly potent triazoleantifungal agents with piperidine-oxadiazole side chains

Abstract

Due to increasing incidence and mortality of invasive fungal infections, discovery and development of new generations of antifungal agents represents a challenging task. On the basis of our previously reported triazole-benzyloxypiperidinyl lead compound, a series of novel triazole antifungal agents containing piperidine-oxadiazole side chains were rationally designed and synthesized. Most of the target compounds showed excellent inhibitory activity against clinically important fungal pathogens. In particular, compounds 6g (MIC = 0.031 μg mL⁻¹) and 11b (MIC = 0.016 μg mL⁻¹) were highly active against Candida albicans including fluconazole-resistant strains. Moreover, they showed inhibitory activity against hyphal formation with low toxicity, which were promising leads for further development.