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

Abstract

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.