Isolation and Identification of Novel Antioxidant Polyketides from an Endophytic Fungus Ophiobolus cirsii LZU-1509

Sixteen
new polyketides, ophicirsins A–P (1–16),
including four novel carbon skeletons (5–9, 14, 15, and 16), were isolated
from the extract of an endophytic fungus Ophiobolus
cirsii LZU-1509. The unique frameworks of ophicirsin
N (14) and O (15) feature a different cyclic
ether connected with an aromatic ring system. Ophicirsin P (16) is characterized by the unprecedented heterozygote of
a polyketide and an alkaloid. The absolute stereochemistries of those
polyketides were characterized via single-crystal X-ray diffraction
analysis and the experimental and computational electric circular
dichroism spectra comparison. Theoretical reaction pathways in the
fermentation to generate different novel skeletons starting from acetyl
CoA and malonyl CoA helped to assign their structures. Compounds 1–16 appear almost nontoxic in HepG2 and HT-1080 tumor
cells. Their antioxidant effects were further evaluated, and 15 exhibits an excellent protection activity in hydrogen peroxide-stimulated
oxidative damage in neuron-like PC12 cells via screening all compounds.
Moreover, 15 displays a greater ability to scavenge the
2,2-diphenyl-1-picrylhydrazyl free radicals than resveratrol. Taken
together, these findings suggest that the novel polyketides could
serve as potential antioxidant agents for neuroprotection.