Immunosuppressive Breviane Spiroditerpenoids from Penicillium bialowiezense Isolated from a Medicinal Plant

Breviane spiroditerpenoids are a small group of structurally interesting and complex meroterpenoids. This work focused on an endophytic fungus Penicillium bialowiezense ZBWPQ-27 that was isolated from a medicinal plant Euphorbia neriifolia, leading to the isolation of 15 breviane spiroditerpenoids with four types of polycyclic systems (1–6 and 9–17), and two new carotane sesquiterpenoids (7 and 8). The structures including absolute configurations of the new compounds 1–8 were elucidated by spectroscopic data analysis and electronic circular dichroism (ECD) calculations. In addition, the misassigned NMR data of several resonances of the 5-methyl-TAL motif (E ring) in those of known brevianes (9–15) were corrected by spectroscopic data analysis. Biological tests revealed that brevianes with the type A ring system (6/6/6/5/6) showed moderate to significant immunosuppressive activities, and compound 11 displayed the most potent inhibitory activities against concanavalin A (ConA)-induced T cell proliferation (IC50 4.1 ± 0.2 μM) and lipopolysaccharide (LPS)-induced B cell proliferation (IC50 4.6 ± 0.2 μM), with good SI values of 28 ± 2 and 25 ± 4, respectively.