Chemical Investigation of Marine-Derived Fungus Aspergillus flavipes for Potential Anti-Inflammatory Agents

Abstract

The marine fungus, Aspergillus flavipes (MTCC 5220), was isolated from the pneumatophore of a mangrove plant Acanthus ilicifolius found in Goa, India. The crude extract of A. flavipes was found to show anti-inflammatory activity. It blocked interleukin-6 (IL-6) and tumor necrosis factor-? (TNF-?) production in lipopolysaccharide (LPS)-activated THP-1 cells with IC50 of 2.69�0.5??M and 6.64�0.4??M, respectively. The chemical investigation led to the isolation of optically inactive 4?-[(1E)-propen-1-yl]cyclopentane-1?,2?-diol (1) along with a new optically active diastereoisomeric compound, 4?-[(1E)-propen-1-yl]cyclopentane-1?,2?-diol (2). In addition, the fungus also produced known compounds (+)-terrein (3), butyrolactone I (4) and butyrolactone II (5) in high yields. Among these, (+)-terrein (3) exhibited IL-6 and TNF-? inhibition activity with IC50 of 8.5�0.68??M and 15.76�0.18??M, respectively, while butyrolactone I (4) exhibited IC50 of 12.03�0.85??M (IL-6) and 43.29�0.76??M (TNF-?) inhibition activity with low toxicity to host cells in LPS stimulated THP-1 cells. This is the first report of the isolation and characterization of 4?-[(1E)-propen-1-yl]cyclopentane-1?,2?-diol (2). The structures of all the isolated compounds were elucidated on the basis of extensive detailed NMR spectroscopic data. Anti-inflammatory activity of the fungi A. flavipes is presented here for the first time, which was due to (+)-terrein and butyrolactone I, as the major constituents and they can be further explored in the therapeutic area.