Drimane-type sesquiterpenoids from aspergillus keveioides under OSMAC strategy characterized by GNPS possess in vitro antitumor cytotoxicity: A combined approach of bioactivity assay and network pharmacology.

Abstract

Guided by LC-MS/MS and Global Natural Products Social Molecular Networking (GNPS), two new drimane-type sesquiterpenoids, ustusolates H and I, along with eleven known analogues, were isolated from the fermentation broth of Aspergillus keveioides. Their chemical structures were elucidated on the basis of comprehensive spectroscopic data. All isolated compounds were assessed for cytotoxicity against four human cancer cell lines, including HeLa, BGC-823, HCT-116 and MIAPaCa-2. Compound 7 exerted potent inhibitory activity toward BGC-823 and MIAPaCa-2 cells, while compound 11 showed remarkable cytotoxic effects against BGC-823 and HCT-116 cells. Further combined with network pharmacology, we screened potential drug targets and explored the binding modes via molecular docking. This study not only expands the chemical diversity of fungal drimane-type sesquiterpenoids, but also provides a theoretical basis for further research and exploitation of this class of metabolites.