title: Ceylonamides A-F, Nitrogenous Spongian Diterpenes That Inhibit RANKL-Induced Osteoclastogenesis, from the Marine Sponge Spongia ceylonensis.
abstract: 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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kumamoto University , Oe-honmachi 5-1, Kumamoto 862-0973, Japan.
authors.forename: Ahmed H
authors.initials: AH
authors.lastname: El-Desoky
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kumamoto University , Oe-honmachi 5-1, Kumamoto 862-0973, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Kato
authors.affiliation: Faculty of Fisheries and Marine Science, Sam Ratulangi University , Kampus Bahu, Manado 95115, Indonesia.
authors.forename: Esther D
authors.initials: ED
authors.lastname: Angkouw
authors.affiliation: Faculty of Fisheries and Marine Science, Sam Ratulangi University , Kampus Bahu, Manado 95115, Indonesia.
authors.forename: Remy E P
authors.initials: RE
authors.lastname: Mangindaan
authors.affiliation: Naturalis Biodiversity Center , P.O. Box 9517, 2300 RA Leiden, The Netherlands.
authors.forename: Nicole J
authors.initials: NJ
authors.lastname: de Voogd
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kumamoto University , Oe-honmachi 5-1, Kumamoto 862-0973, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Tsukamoto
mesh_terms: D000818:Animals; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects*; D008386:Marine Biology; D051379:Mice; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010012:Osteogenesis / Q000187:drug effects*; D011161:Porifera / Q000737:chemistry*; D053245:RANK Ligand / Q000494:pharmacology*; D000067996:RAW 264.7 Cells; D013329:Structure-Activity Relationship
chemical_list: D004224:Diterpenes; D053245:RANK Ligand; C000617491:ceylonamide A; C000617492:ceylonamide B