Penispirolactam and penipyrroloindole, two unusual polycyclic indole diterpenoids with anti-hepatic fibrosis activity from the endophytic fungus Penicillium janthinellum H-6

Penispirolactam (1) and penipyrroloindole (2), two highly modified paspaline-type indole diterpenoids (IDTs), along with three new (3–5) and two known (6 and 7) paspaline-type IDTs were obtained from the endophytic fungus Penicillium janthinellum H-6 guided by liquid chromatography-mass spectrometry (LC-MS)-based molecular network. Architecturally, penispirolactam (1) possesses a unique octacyclic skeleton (6/5/6/6/5/6/6/6) with a spiro core formed by the integration of a C₆–C₂ unit with the indole moiety, and penipyrroloindole (2) represents a rearranged octacyclic skeleton (6/5/6/5/5/6/6/6) with a pyrrolo[1,2-a]indole core fragment. Their structures, including absolute configurations, were established by detailed spectroscopic analysis, gauge-independent atomic orbital (GIAO) 1D nuclear magnetic resonance (NMR) (DP4+) calculation protocol, and electronic circular dichroism (ECD) calculation method. The plausible biosynthetic pathway of compounds 1 and 2 was also speculated. Additionally, the anti-hepatic fibrosis activity of all compounds was explored, and it was found that 1 could exert its effects by inhibiting the transforming growth factor-β (TGF-β)/Smad signaling pathway without cytotoxicity.