Ceylonamides A–F, nitrogenous spongian diterpenes that inhibit RANKL-induced osteoclastogenesis, from the marine sponge Spongia ceylonensis

Seven new spongian diterpenes, ceylonamides A–F (1–6) and 15α,16-dimethoxyspongi-13-en-19-oic acid (7), were isolated from the Indonesian marine sponge Spongia ceylonensis along with eight known spongian diterpenes, 8–15. Compounds 1–6 were determined to be nitrogenous spongian diterpenes. The isolated compounds were examined for the inhibition of RANKL-induced osteoclastogenesis in RAW264 macrophages. Ceylonamide A (1) exhibited the most potent inhibitory activity with an IC50 value of 13 μM, followed by ceylonamide B (2) (IC50, 18 μM). An examination of the structure–activity relationships of the isolated compounds revealed that the position of the carbonyl group of the γ-lactam ring and bulkiness of the substituent at its nitrogen atom were important for inhibitory activity.