Undescribed Pneumocandin Analogues From Glarea lozoyensis and Evaluation of Their Antifungal Activity.

Caspofungin is an antifungal agent used for the treatment of severe fungal infections, which is semi-synthesized from pneumocandin B0, a secondary metabolite produced by filamentous fungus Glarea lozoyensis. To identify new pneumocandin analogues, a chemical reinvestigation was carried out on G. lozoyensis. This endeavor resulted in the isolation of pneumocandin B0 and two previously undescribed pneumocandin derivatives, designated as pneumocandins B7 and B8. Their structures were elucidated using HRESIMS and NMR spectroscopic analyses. Pneumocandins B7 and B8 represent the first reported pneumocandin analogues with a hydroxylated 10,12-dimethylmyristate (DMM) moiety. Antifungal activity assays revealed that pneumocandins B7 and B8 exhibited reduced antifungal efficacy across all eight tested Candida strains in comparison to pneumocandin B0. These findings suggest that the introduction of a hydroxyl group in the DMM moiety has a negative effect on the antifungal activity. These results enrich the structural diversity of the pneumocandin family and provide new insights into the structure-activity relationship of pneumocandins.