Engineering hypoxia-responsive 6-aminonicotinamide prodrugs for on-demand NADPH depletion and redox manipulation.

Glucose-6-phosphate dehydrogenase (G6PD) is a promising target in cancer therapy. However, poor cellular uptake and off-target toxicity have impeded the clinical translation of a canonical G6PD inhibitor (6-aminonicotinamide/6AN). Here, we report a prodrug strategy to address this issue.

Molecular networking-driven isolation of 8'-Glycosylated biscoumarins from Cruciata articulata.

A molecular networking-guided phytochemical investigation of Cruciata articulata led to the isolation of five unreported biscoumarins, four of which were characterized by a shared 6-methoxy-7,8'-dihydroxy-3,7'-biscoumarin aglycone. These were isolated alongside two known coumarin glycosides, daphnetin-8-O-β-D-glucoside and 6'-acetoxy-daphnetin-8-O-β-D-glucoside. Their structures were elucidated by extensive 1D and 2D NMR experiments, in combination with chemical transformation and MS/MS fragmentation analysis.