Immunosuppressive Breviane Spiroditerpenoids from <i>Penicillium\nbialowiezense</i> Isolated from a Medicinal Plant

Breviane\nspiroditerpenoids are a small group of structurally interesting\nand complex meroterpenoids. This work focused on an endophytic fungus <i>Penicillium bialowiezense</i> ZBWPQ-27 that was isolated from\na medicinal plant <i>Euphorbia neriifolia</i>, leading to\nthe isolation of 15 breviane spiroditerpenoids with four types of\npolycyclic systems (<b>1</b>–<b>6</b> and <b>9</b>–<b>17</b>), and two new carotane sesquiterpenoids\n(<b>7</b> and <b>8</b>). The structures including absolute\nconfigurations of the new compounds <b>1</b>–<b>8</b> were elucidated by spectroscopic data analysis and electronic circular\ndichroism (ECD) calculations. In addition, the misassigned NMR data\nof several resonances of the 5-methyl-TAL motif (E ring) in those\nof known brevianes (<b>9</b>–<b>15</b>) were corrected\nby spectroscopic data analysis. Biological tests revealed that brevianes\nwith the type A ring system (6/6/6/5/6) showed moderate to significant\nimmunosuppressive activities, and compound <b>11</b> displayed\nthe most potent inhibitory activities against concanavalin A (ConA)-induced\nT cell proliferation (IC<sub>50</sub> 4.1 ± 0.2 μM) and\nlipopolysaccharide (LPS)-induced B cell proliferation (IC<sub>50</sub> 4.6 ± 0.2 μM), with good SI values of 28 ± 2 and\n25 ± 4, respectively.