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Xanthone Inhibitors of Unfolded Protein Response Isolated from Calophyllum caledonicum
Marine Chambaud1, Anne-Marie Le Ray1, Racha Hamzi1
1SONAS | Substances d'Origine Naturelle et Analogues Structuraux Univ Angers, SONAS, SFR QUASAV, F-49000 Angers, France.
Abstract:
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.
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