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‐α (TNF‐α) production in lipopolysaccharide (LPS)‐activated THP‐1 cells with IC50 of 2.69±0.5 μM and 6.64±0.4 μM, respectively. The chemical investigation led to the isolation of optically inactive 4β‐[(1E)‐propen‐1‐yl]cyclopentane‐1β,2β‐diol (1) along with a new optically active diastereoisomeric compound, 4β‐[(1E)‐propen‐1‐yl]cyclopentane‐1β,2α‐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‐α inhibition activity with IC50 of 8.5±0.68 μM and 15.76±0.18 μM, respectively, while butyrolactone I (4) exhibited IC50 of 12.03±0.85 μM (IL‐6) and 43.29±0.76 μM (TNF‐α) 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 4β‐[(1E)‐propen‐1‐yl]cyclopentane‐1β,2α‐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.

Investigation of Secondary Metabolites from Marine‐Derived FungiAspergillus

“…Preparation of butyrolactone III (3) and aspernolide Q (5) : The major compound, butyrolactone I (2) was purified and obtained as colorless crystalline solid. Its structure was confirmed by NMR data and compared with our previous data published [16] . To confirm the structures of butyrolactone III (4) and aspernolide Q (5) , both compounds were prepared using butyrolactone I (2) as starting material.…”

“…According to various reports, these molecules exhibit promising biological activities. In our previous investigation, we have revealed an anti‐inflammatory activities of these compounds [16] . (+)‐Terrein displayed anti‐inflammatory activity witht IC 50 8.5 μM (IL‐6) and 15.76 μM (TNF‐ α ), While, butyrolactone I, exhibited IC 50 12.03 μM (IL‐6) and 43.29 μM (TNF‐ α ).…”

“…Its structure was confirmed by NMR data and compared with our previous data published. [16] To confirm the structures of butyrolactone III (4) and aspernolide Q (5), both compounds were prepared using butyrolactone I (2) as starting material. The treatment of butyrolactone I (2) with mCPBA in anhydrous DCM yielded butyrolactone III (4) in 78 % yield.…”

“…In our previous investigation, we have revealed an anti-inflammatory activities of these compounds. [16] (+)-Terrein displayed anti-inflammatory activity witht IC 50 8.5 μM (IL-6) and 15.76 μM (TNF-α), While, butyrolactone I, exhibited IC 50 12.03 μM (IL-6) and 43.29 μM (TNF-α). It has been reported that (+)-Terrein displayed significant anticancer activities against different cancer lines.…”

“…These work demonstrated the capabilities of tandem mass spectrometry in identification of related compounds which are produced in trace quantity by the organisms without any prior chromatographic purification. Earlier we have isolated and characterized various metabolites, aspernolides A‐B [15] , 4 β ‐[(1 E )‐propen‐1‐yl] cyclopentane‐1 β ,2 β ‐diol and its diastereoisomer, 4 β ‐[(1 E )‐propen‐1‐yl]cyclopentane‐1 β ,2 α ‐diol, (+)‐terrein, butyrolactone I–II and physcion from Aspergillus fungi [16] . However, we may have missed identification of several metabolites from both the cultures and hence, we made an effort of identifying those molecules using ESI‐MS and collision induced dissociation (CID)‐MS/MS studies.…”