Brominated Azaphilones from the Sponge-Associated Fungus Penicillium canescens Strain 4.14.6a

Journal of Natural Products
2019.0

Abstract

The fungus <i>Penicillium canescens</i> was isolated from the inner tissue of the Mediterranian sponge <i>Agelas oroides</i>. Fermentation of the fungus on solid rice medium yielded one new chlorinated diphenyl ether (<b>1</b>) and 13 known compounds (<b>2</b>-<b>14</b>). Addition of 5% NaBr to the rice medium increased the amounts of <b>4</b>-<b>6</b>, while lowering the amounts of <b>8</b>, <b>12</b>, and <b>14</b>. Furthermore, it induced the accumulation of <b>17</b> and two new brominated azaphilones, bromophilones A and B (<b>15</b> and <b>16</b>). Compounds <b>15</b> and <b>16</b> are the first example of azaphilones with the connection of a benzene moiety and the pyranoquinone core through a methylene group. The structures of the new compounds were elucidated based on the 1D and 2D NMR spectra as well as on HRESIMS data. The absolute configuration of the condensed bicyclic moiety of <b>15</b> and <b>16</b> was determined by sTDA ECD calculations. Compound <b>16</b> exhibited moderate cytotoxicity against the mouse lymphoma cell line L5178Y (IC<sub>50</sub> 8.9 μM), as well as against the human ovarian cancer cell line A2780 (IC<sub>50</sub> 2.7 μM), whereas the stereoisomer <b>15</b> was considerably less active.

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