Ellagic acid C and aspergone R, two undescribed pyrones from the endophytic fungus <i>Diaporthe</i> sp. CB10100: biological evaluation, molecular docking and molecular dynamics studies

Two new compounds, ellagic acid C (<b>5</b>) and aspergone R (<b>6</b>), along with four previously identified compounds (<b>7-10</b>), were successfully isolated from the fungus <i>Diaporthe</i> sp. CB10100. Ellagic acid C (<b>5</b>) contains an uncommon tricyclic 5/6/6 ring system. A biosynthetic pathway for <b>6</b> was proposed, although additional investigations are needed to elucidate the ethyl biosynthesis mechanism. Both aspergone R (<b>6</b>) and (-)-terpestacin (<b>9</b>) decreased lipopolysaccharide (LPS)-induced protein expression of iNOS and COX-2. Molecular docking analysis revealed that <b>6</b> and <b>9</b> potentially interact with the active sites of iNOS and COX-2. Molecular dynamics simulations demonstrated that, compared with the other compounds, <b>6</b> exhibited increased binding stability and stronger interactions with the COX-2 protein. Furthermore, <b>5-9</b> were effective against MRSA, <i>Klebsiella pneumoniae</i>, and <i>Mycolicibacterium</i> (<i>Mycobacterium</i>) smegmatis, with MICs greater than 64 μg/mL. These findings suggest that <b>6</b> and the common γ-pyrone scaffold could serve lead compounds for anti-inflammatory drug development.