Structure-guided design and synthesis of C22- and C32-modified FK520 analogs with enhanced activity against human pathogenic fungi.

ABSTRACT: Invasive fungal infections are a leading cause of death worldwide. Translating molecular insights into clinical benefits is challenging because fungal pathogens and their hosts share similar eukaryotic physiology. Consequently, current antifungal treatments have limited efficacy, may be poorly fungicidal in the host, can exhibit toxicity, and are increasingly compromised by emerging resistance. We have established that the phosphatase calcineurin (CaN) is required for invasive fungal disease and an attractive target for antifungal drug development. CaN is a druggable target, and there is vast clinical experience with the CaN inhibitors FK506 and cyclosporin A (CsA). However, while FK506 and its natural analog FK520 exhibit antifungal activity, they are also immunosuppressive in the host an

SUBMITTER: Dome PA 

PROVIDER: S-EPMC11725869 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature