Unusual Diterpenoids from the South China Sea Soft Coral Sarcophyton ehrenbergi

Sarcobergilide A ( 1 ), featuring an uncommon 11/7/5 tricyclic ring system, a new flexibilane-based diterpenoid, sarcoberginol A ( 2 ), and seven new cembranoids 3–9 were isolated from the South China Sea soft coral Sarcophyton ehrenbergi . The structures of the new compounds were established by extensive spectroscopic analyses, X-ray diffraction, the quantum mechanical NMR (QM-NMR) method, and electronic circular dichroism (ECD) calculations. A plausible biosynthetic pathway for 1 was proposed. In the bioassays, a primary screen in LPS-stimulated RAW264.7 macrophages highlighted compound 3 as the most active compound, showing the greatest reduction of NO release and TNFα secretion among the isolates. In TNFα-stimulated MC38 cells, RNA-seq analysis showed that compound 3 downregulated inflammation- and immune-related transcriptional programs and dose-dependently mitigated TNFα-induced IκBα degradation, consistent with attenuation of TNFα-associated inflammatory signaling. Moreover, several compounds exhibited moderate inhibitory effects against six pathogenic bacterial strains, with MIC values ranging from 2 to 64 μg/mL.