Novel oxabicyclo[2.2.1]heptane-3-one derivatives with NO inhibitory and cytotoxic activities, and xanthone derivatives from the endolichenic fungus Exophiala sp

Abstract

Eight new compounds (1-8) featuring an unusual oxabicyclo[2.2.1]heptane-3-one moiety, along with three new xanthone-type compounds (11-13), were isolated from the culture extracts of the endolichenic fungus Exophiala sp., which lives in symbiosis with the lichen Parmotrema tinctorum. Molecular networking analysis of the culture extract revealed clusters containing nodes with unknown molecular weights with a distinct UV pattern, prompting targeted isolation through chromatographic techniques. Compounds 1-6 feature a unique 2- oxabicyclo[2.2.1]heptane-3-one core linked to a linear methyl-hexatriene and a trimethyl-cyclopentanone moiety. Their structures were completely established by spectroscopic methods combined with computer calculations. In contrast, compounds 7 and 8, which lack the cyclized trimethyl-cyclopentanone moiety seen in 1-6, were found to be unstable and degraded after NMR analysis, preventing the determination of their final stereochemistry. Although similar structural frameworks have been reported in two previous studies, compounds 1-8 differ in the stereochemistry at C-6 and C-13. Additionally, the newly identified xanthone-type new compounds (11-13) exhibit diverse prenyl group modifications. Biological evaluation of the isolated compounds revealed that compound 1 exhibited the strongest NO inhibitory activity, with an IC₅₀ value of 21 μg/mL.

Keywords: Endolichenic fungi; Exophiala sp.; Molecular networking; Oxabicyclo[2.2.1]heptane-3-one; Parmotrema tinctorum; Xanthone.