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.

Marine Natural Products from Indonesian Waters

“…Therefore, the current primary issues in marine conservation, such as the loss of biodiversity through over-exploitation and habitat degradation, can be overcome. Additional information can be found in the Supplementary Materials [95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127,128,129,130,131,132,133,134,135,136,137,138,139,140,141,142,143,144,145,146,147,148,149,150,151,152,153,154,…”

Marine natural products

“…Geodiataurine exhibited weak activity (IC 50 ¼ 8.5 mM) against A2058 melanoma cells but with no antibacterial effects. 454 Other diterpenoids, 949 and 950 (total syntheses also achieved), 455 especially based upon the ubiquitous spongian diterpene skeleton 951-962, [456][457][458] were isolated from Theonella, Dysidea, Spongia and Dendrilla sponges, all with varying activities. Several norscalarane 963-967 (ref.…”

Cytotoxicity of New Diterpene Alkaloids, Ceylonamides G-I, Isolated From Indonesian Marine Sponge of Spongia sp.

“…The Electrospray Ionization Time of Flight Mass Spectrometry (ESI-TOF-MS) of 1 showed a quasi-molecular ion peak [M + Na] + at m/z 354, and the molecular formula was determined as C 20 H 29 NO 3 by high-resolution (HR)-ESI-TOF-MS. 1 H- and 13 C-Nuclear Magnetic Resonance (NMR) spectra of 1 showed the characteristic signals of terpenes, 3 methyl signals [δ H 1.19 (3H, s), δ C 22.4 (C-17); δ H 1.21 (3H, s), δ C 29.3 (C-18); δ H 0.89 (3H, s), δ C 14.7 (C-20)], 2 carbonyl carbon signals [δ C 177.4 (C-16) and δ C 183.8 (C-19)], and 2 olefin carbon signals [δ C 129.2 (C-13) and δ C 166.5 (C-14)]. In addition, NMR spectra of 1 were similar to those of ceylonamide F. 4,12 Marked differences in the chemical shifts of the carbon atoms in these compounds were observed at δ C 22.8 (C-12), δ C 129.2 (C-13), δ C 166.5 (C-14), δ C 45.6 (C-15), and δ C 177.4 (C-16) for 1 and at δ C 27.4 (C-12), δ C 154.1 (C-13), δ C 141.3 (C-14), δ C 176.4 (C-15), and δ C 49.2 (C-16) for 4 (Tables 1 and 2). Then, the Heteronuclear Multiple Bond Correlation (HMBC) correlations between δ H 2.05, 2.32 (H-12) and δ C 129.2 (C-13), δ C 177.4 (C-16); δ H 3.85, 3.95 (H-15) and δ C 129.2 (C-13), δ C 166.5 (C-14), δ C 177.4 (C-16); δ H 1.19 (H-17) and δ C 166.5 (C-14) indicated that the γ-lactam ring of 1 had the opposite orientation to that of 4 (Figures 1 and 2).…”

“…13 On the other hand, the specific rotations of compounds 1 to 3 were also negative (−24, −23, and −32, respectively) and were similar to the reported specific rotations of ceylonamides A-F (−26, −29, −26, −38, −23, and −110, respectively). 12 The absolute stereochemistry of compounds 1 to 3 are illustrated in Figure 1. The absolute configuration of ceylonamide F ( 4 ) was also determined on the basis of the specific rotations of spongolactams.…”