Cytotoxic Pentacyclic Benzoquinone Dimers Featuring a Cyclopropane-Bridged Cage-like Skeleton from Penicillium hispanicum

Two new pairs of pentacyclic benzoquinone enantiomers, (±)-penuinones A (1a/1b) and B (2a/2b), were isolated from the mangrove-derived fungus Penicillium hispanicum LA032 using LC-MS/MS-based molecular networking. The structures of new compounds were elucidated by spectroscopic analyses and quantum chemical ECD calculations. Structurally, compounds 1a/1b and 2a/2b possess a highly constructed 6/3/5/6/6 pentacyclic structure featuring a rare cyclopropane-bridged cage-like tricyclo[3.2.1.02,7]octane core skeleton. In addition, a plausible biogenetic pathway of 1a/1b and 2a/2b was proposed. All four compounds exhibited significant cytotoxicity against Hepa1–6 and Huh7 cell lines. Among them, compound 1b exhibited the most potent cytotoxicity against Hepa1–6 and Huh7 cell lines with IC50 values of 1.4 ± 0.44 and 3.0 ± 0.13 μM, respectively.