Cinerols L-R, Anti-inflammatory Meroterpenoids from the Marine Sponge Dysidea cinerea.

Abstract

Seven new sesquiterpene hydroquinone/quinone (SQ) meroterpenoids, cinerols L-R (1-7), along with four known analogues (8-11), were identified from a marine sponge, Dysidea cinerea, collected from the shore of the Xisha Islands in the South China Sea. The structures of 1-7 were established by the analysis of NMR, high-resolution MS, and comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. Cinerol L (1) is particularly noteworthy, as it features a 5H-pyrrolo[1,2a]-benzimidazole moiety modified by an ethyl sulfonate, while cinerols N (3) and O (4) possess a unique acetyl-substituted hydroquinone moiety. Cinerols L-R (1-7) were evaluated for their inhibitory activity against inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and prostaglandin E2 (PGE₂) with IC₅₀ values of 5-20 μM in lipopolysaccharide (LPS)-induced RAW 264.7 mouse macrophages. Furthermore, the potent inhibitory activity on inflammatory cytokines of 4 prompted us to evaluate its effect on the nuclear factor-κB (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathway, a critical pathway that contributes to the inflammatory responses. Cinerol O (4) was unveiled to inhibit cyclooxygenase-2 (COX-2) expression and the production of inflammatory cytokines via suppressing the expression of NF-κB and MAPKs in LPS-induced RAW 264.7 macrophages.