Two New Alkaloids and a New Butenolide Derivative from the Beibu Gulf Sponge-Derived Fungus Penicillium sp. SCSIO 41413

Abstract

Marine sponge-derived fungi have been proven to be a prolific source of bioactive natural products. Two new alkaloids, polonimides E (<b>1</b>) and D (<b>2</b>), and a new butenolide derivative, eutypoid F (<b>11</b>), were isolated from the Beibu Gulf sponge-derived fungus, <i>Penicillium</i> sp. SCSIO 41413, together with thirteen known compounds (<b>3</b>-<b>10</b>, <b>12</b>-<b>16</b>). Their structures were determined by detailed NMR, MS spectroscopic analyses, and electronic circular dichroism (ECD) analyses. Butenolide derivatives <b>11</b> and <b>12</b> exhibited inhibitory effect against the enzyme PI3K with IC₅₀ values of 1.7 μM and 9.8 μM, respectively. The molecular docking was also performed to understand the inhibitory activity, while <b>11</b> and <b>12</b> showed obvious protein/ligand-binding effects to the PI3K protein. Moreover, <b>4</b> and <b>15</b> displayed obvious inhibitory activity against LPS-induced NF-κB activation in RAW264.7 cells at 10 µM.