Chemical constituents from the latex of Garcinia parvifolia and their anti-Unfolded Protein Response activity

Abstract

Inhibition of the Unfolded Protein Response (UPR) pathway of phytopathogenic fungi represents a promising strategy for the discovery of natural products capable of attenuating fungal resistance to plant defense metabolites. Polyprenylated xanthones isolated from Clusiaceae and Calophylaceae have recently been identified as inhibitors of this fungal resistance pathway whereas Garcinia parvifolia (Miq.) Miq. is known for its high xanthone content. Consequently, systematic phytochemical investigation of the latex and bioguided fractionation based on anti-UPR cell-based assay were conducted. A total of sixteen compounds were isolated, including one previously unreported terpenophenol with an original structure (2) and three previously undescribed xanthones (12-14), the latter obtained through bioguided fractionation. Among the isolated compounds, demethylrubraxanthone (12) exhibited notable anti-UPR activity, with an IC₅₀ value of 8.0 ± 0.3 μM. To address the limited availability of (12) in the latex, a semisynthesis from rubraxanthone (1) was eventually conducted.

Keywords: Bioguided fractionation; Clusiaceae; Crop protection; Demethylrubraxanthone; Garcinia parvifolia; Phytochemical analysis; Plant pathogenic fungi; UPR inhibitors; Xanthones.