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

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