Asperunguisins A-F, Cytotoxic Asperane Sesterterpenoids from the Endolichenic Fungus Aspergillus unguis

Six new asperane-type sesterterpenoids, asperunguisins A-F (1-6), were isolated from the endolichenic fungus Aspergillus unguis, together with a known analogue, aspergilloxide (7); these are rare asperane-type sesterterpenoids, characterized by a unique hydroxylated 7/6/6/5 tetracyclic system. The structures of asperunguisins A-F (1-6) were elucidated on the basis of spectroscopic methods (NMR and HRESIMS), X-ray single-crystal diffraction analysis, ECD calculations, and biogenetic considerations. Asperunguisin C (3) showed cytotoxicity against the human Cancer cell line A549 with an IC₅₀ value of 6.2 μM. Further investigation revealed that the observed cell death was a result of G0/G1 cell cycle arrest via DNA damage followed by cellular Apoptosis.