Separation and configurational assignment of stereoisomeric phenalenones from the marine mangrove-derived fungus Penicillium herquei MA-370

Abstract

Eight phenalenone derivatives, including four new compounds, aceneoherqueinones A and B (1 and 2), (+)-aceatrovenetinone A (3a), and (+)-aceatrovenetinone B (3d), along with four known congeners, (–)-aceatrovenetinone A (3b), (–)-aceatrovenetinone B (3c), (–)-scleroderolide (4a), and (+)-scleroderolide (4b), were characterized from the marine mangrove-derived fungus Penicillium herquei MA-370. Among them, compounds 1 and 2 are rare phenalenone derivatives featuring cyclic ether unit between C-5 and C-2′. All of these compounds were subjected to chiral HPLC analysis, and the unstable stereoisomers 3a–3d, containing configurationally labile chirality centers, were characterized by online HPLC-ECD measurements supported with TDDFT-ECD calculations. The structures of these compounds were elucidated by detailed analysis of their NMR and mass spectroscopic data, and the absolute configuration of compound 1 was confirmed by X-ray diffraction analysis, while those of compounds 2 and 3a–3d were determined by TDDFT-ECD calculations of their ECD spectra. All of the isolated compounds were tested for the inhibitory activity against angiotensin-I-converting enzyme (ACE), and compounds 1 and 2 displayed activity with IC50 values 3.10 and 11.28 μM, respectively. The intermolecular interaction and potential binding sites of 1 and 2 with ACE were elaborated by molecular docking, showing that compound 1 bound well with ACE via hydrogen interactions with residues Ala261, Gln618, Trp621, and Asn624, while compound 2 interacted with residues Asp358 and Tyr360.