Promising antifungal properties of the orally active autophagy inhibitor SBP-7455 against fluconazole-resistant Candida clinical isolates.

This article investigates the antifungal properties of SBP-7455, a novel dual autophagy inhibitor targeting unc-51-like autophagy activating kinase 1 (ULK1) and ULK2, against fluconazole-resistant Candida species, which are major opportunistic fungal pathogens. SBP-7455 demonstrated inhibitory effects on both a fluconazole-resistant standard Candida albicans strain and six fluconazole-resistant clinical Candida isolates, with minimum inhibitory concentrations (MICs) ranging from 5.48 to 87.82 µM. When combined with fluconazole, SBP-7455 restored fluconazole sensitivity in resistant strains, whereas its combination with chloroquine was antagonistic. Mechanistically, SBP-7455 disrupted Candida cell membrane integrity and increased reduced glutathione levels, suggesting induction of oxidative stress through autophagy inhibition. These findings highlight SBP-7455 as a promising candidate for further development against resistant Candida infections, particularly in immunocompromised patients.