Background: Endophytic fungi are being recognized as vital and untapped sources of a
variety of structurally novel and unique bioactive secondary metabolites in the field of natural products
drug discovery. Herein, this study reports the isolation and characterization of secondary metabolites
from an endophytic fungus Penicillium polonicum (NFW9) associated with Taxus fuana.
Method: The extracts of the endophytic fungus cultured on potato dextrose agar were purified using
several chromatographic techniques. Biological evaluation was performed based on their abilities to
inhibit tumor necrosis factor-alpha (TNF-α)-induced nuclear factor-kappa B (NF-κB) and cytotoxicity
Results: Bioactivity-directed fractionation of the ethyl acetate extract of a fermentation culture of an
endophytic fungus, Penicillium polonicum led to the isolation of a dimeric anthraquinone, (R)-
1,1',3,3',5,5'-hexahydroxy-7,7'-dimethyl[2,2'-bianthracene]-9,9',10,10'-tetraone (1), a steroidal furanoid
(-)-wortmannolone (2), along with three other compounds (3−4). Moreover, this is the first report
on the isolation of compound 1 from an endophytic fungus. All purified metabolites were characterized
by NMR and MS data analyses. The stereo structure of compound 1 was determined by the
measurement of specific optical rotation and CD spectrum. The relative stereochemistry of 2 was
confirmed by single-crystal X-ray diffraction. Compounds 2−3 showed inhibitory activities in the
TNF-α-induced NF-κB assay with IC50 values in the range of 0.47−2.11 µM. Compounds 1, 4 and 5
showed moderate inhibition against NF-κB and cancer cell lines.
Conclusion: The endophytic fungus Penicillium polonicum of Taxus fuana is capable of producing
biologically active natural compounds. Our results provide a scientific rationale for further chemical
investigations into endophyte-producing natural products, drug discovery and development.