Chemical Constituents of the Endophytic Fungus Hypoxylon sp.12F0687 Isolated from Taiwanese Ilex formosana

Bioassay-guided fractionation of an AcOEt-soluble fraction of the liquid fermentation of an endophytic fungus Hypoxylon sp. BCRC 12F0687 associated with the root of Taiwanese Ilex formosana (Aquifoliaceae) resulted in the isolation of two new compounds, i.e., one benzenoid, hypoxyphenone (1), and one azaphilone derivative, hypoillexidiol (2), two metabolites isolated for the first time from natural source, (-)-(3S)-3-hydroxy-3-methyloxindole (3) and (+)-vermelone (4), along with twelve previously identified compounds, 5-16. Their structures were determined through in-depth spectroscopic and mass-spectrometric analyses. The effects of some isolates on the inhibition of NO and IL-6 production in lipopolysaccharide-activated RAW 264.7 murine macrophages were evaluated. Of the isolates, 2 and 3 exhibited potent anti-NO production activity, with IC50 values of 17.5 +/- 1.8 and 24.7 +/- 1.6M, respectively, compared to that of quercetin, an iNOS inhibitor with an IC50 value of 35.9 +/- 1.7M. Compounds 2, 4, 5, and 12 also showed moderate inhibition of IL-6 production, with IC50 values ranging from 27.2 +/- 1.8 to 35.3 +/- 5.8M. This is the first report on an oxindole metabolite from the genus Hypoxylon.