Aspertaichamide a, a novel cytotoxic prenylated indole alkaloid possessing a bicyclo[2.2.2]diazaoctane framework from a marine algal-derived endophytic fungus aspergillus taichungensis 299.

Filamentous fungi belonging to the genus Aspergillus are prodigious producers of alkaloids, particularly prenylated indole alkaloids, that often exhibit structurally diversified skeletons and potent biological activities. In this study, five prenylated indole alkaloids possessing a bicyclo[2.2.2]diazaoctane core ring system, including a novel derivative, namely aspertaichamide A (1), as well as four known compounds, (+)-stephacidin A (2), sclerotiamide (3), (-)-versicolamide B (4), and (+)-versicolamide B (5), were isolated and identified from A. taichungensis 299, an endophytic fungus obtained from the marine red alga Gelidium amansii. The chemical structures of the compounds were elucidated by comprehensive NMR and HRESIMS spectroscopic analyses. In addition to the previously reported prenylated indole alkaloids, aspertaichamide A (1) was characterized as having an unusual ring structure with the fusion of a 3-pyrrolidone dimethylbenzopyran to the bicyclo[2.2.2]diazaoctane moiety, which was rare in these kinds of compounds. The absolute configuration of 1 was determined by TDDFT-ECD calculations. In vitro cytotoxic assays revealed that the novel compound 1 possessed selective cytotoxic activity against five human tumor cell lines (A549, HeLa, HepG2, HCT-116, and AGS), with IC50 values of 1.7-48.5 µM. Most importantly, compound 1 decreased the viability of AGS cells in a concentration-dependent manner with an IC50 value of 1.7 µM. Further studies indicated that 1 may induce AGS cells programmed cell death via the apoptotic pathway.

Antimicrobial and cytotoxic phenolic bisabolane sesquiterpenoids from the fungus Aspergillus flavipes 297.

Phenolic bisabolane-type sesquiterpenoids (PBS) represent a rare class of natural products with diverse biological activities. In this study, chemical investigations of the fungus Aspergillus flavipes 297 resulted in the isolation and identification of seven PBS, including a pair of new enantiomers (+)-1a and (-)-1b, a new derivative 2, and five previously reported ones 3-7. The chemical structures of the isolated PBS were determined by extensive NMR and HRESIMS spectroscopic analysis. The absolute configurations of the separated enantiomers (+)-1a and (-)-1b were solved by comparison of the experimental ECD spectra with those of the TDDFT-ECD calculated spectra. The new compounds 1 and 2 represent rare cases of PBS bearing a methylsulfinyl group, which was distinct from the commonly-observed PBS structurally. All the isolated compounds 1-7 were evaluated their antimicrobial and cytotoxic activities. As a result, the tested compounds showed selective antimicrobial activity against several pathogenic bacteria and fungi with the MIC (minimum inhibiting concentrations) values ranging from 2 to 64 µg/mL. Moreover, enantiomers (+)-1a and (-)-1b, together with compound 2, exhibited promising cytotoxicity against MKN-45 and HepG2 cell lines, respectively, indicating that the methylsulfinyl substituent enhanced cytotoxicity to a certain degree.