Xanthone Inhibitors of Unfolded Protein Response Isolated from Calophyllum caledonicum

The unfolded protein response (UPR) is a key component of fungal virulence. The prenylated xanthone γ-mangostin isolated from Garcinia mangostana (Clusiaceae) fruit pericarp, has recently been described to inhibit this fungal adaptative pathway. Considering that Calophyllum caledonicum (Calophyllaceae) is known for its high prenylated xanthone content, its stem bark extract was fractionated using a bioassay-guided procedure based on the cell-based anti-UPR assay. Four previously undescribed xanthone derivatives were isolated, caledonixanthones N–Q (3, 4, 8, and 12), among which compounds 3 and 8 showed promising anti-UPR activities with IC50 values of 11.7 ± 0.9 and 7.9 ± 0.3 μM, respectively.