Dysidaminones A–M, cytotoxic and NF-κB inhibitory sesquiterpene aminoquinones from the South China Sea sponge Dysidea fragilis

Abstract

Dysidaminones A–M (1–13), thirteen new sesquiterpene aminoquinones, along with six known ones (14–19), were isolated from the South China Sea sponge Dysidea fragilis. The new structures were determined by extensive spectroscopic analyses, the absolute configurations of 1 and 2 were determined by single-crystal X-ray diffraction analysis, and the absolute configurations of 3–13 were assigned by comparing their CD spectra with those of 1 and 2. Dysidaminones C (3), E (5), H (8), and J (10), 18-methylaminoavarone (14), and 18-aminoavarone (16) showed cytotoxicity against mouse B16F10 melanoma and human NCI-H929 myeloma, HepG2 hepatoma, and SK-OV-3 ovarian cancer cell lines. In addition, these six cytotoxic compounds also exhibited NF-κB inhibitory activity with IC₅₀ values of 0.05–0.27 μM. Preliminary structure–activity relationship analysis indicated that 18-aminosubstituted sesquiterpene quinones with exocyclic double bond (Δ^4,11) are cytotoxic agents and NF-κB inhibitors.