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 15 alpha,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 mu M, followed by ceylonamide B (2) (IC50, 18 mu M). An examination of the structure activity relationships of the isolated compounds revealed that the position of the carbonyl group of the y-lactam ring and bulkiness of the substituent at its nitrogen atom were important for inhibitory activity.