Placotylene A, an Inhibitor of the Receptor Activator of Nuclear Factor-κB Ligand-Induced Osteoclast Differentiation, from a Korean Sponge Placospongia sp.

Abstract

A new inhibitor, placotylene A (1), of the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation, and a regioisomer of placotylene A, placotylene B (2), were isolated from a Korean marine sponge Placospongia sp. The chemical structures of placotylenes A and B were elucidated on the basis of 1D and 2D NMR, along with MS spectral analysis and revealed as an iodinated polyacetylene class of natural products. Placotylene A (1) displayed inhibitory activity against RANKL-induced osteoclast differentiation at 10 μM while placotylene B (2) did not show any significant activity up to 100 μM, respectively.

Marine natural products

“…With 283 new structures reported from the phylum Porifera in 2014, sponges have returned again to be a dominant source of new bioactive metabolites, although the growing realisation that microbial symbionts are the real producers of "sponge" specialised metabolites highlights the need for more detailed metagenomic and biosynthetic analyses of sponge matrices. Sphingoids 740 504 and 741, 505 taurinated fatty acids 742-745 506,507 and a large number of polyacetylenes 746-765 [508][509][510][511][512][513] have been reported from the genera Callyspongia, Coscinoderma, Echinoclathria, Petrosia, Placospongia, Siphonochalina and Xestospongia. The synthesis of a series of miyakosyne A (Petrosia sp.)…”

Marine natural products

“…711 First total syntheses were reported for many compounds including the lipids motualevic acid F, (E)-and (Z)-antazirine, [712][713][714] mycalol (revised to 1105) [715][716][717] and myrmekioside A, 718,719 and polyacetylenes callyspongynic acid, 720,721 phosphoiodyn A and placotylene A. [722][723][724][725] The structure of plakinidone has been corrected to 1106; the compound is highly sensitive to air oxidation. The compound's relative conguration was also determined, 726,727 while the relative conguration of the C-36 to C-42 portion of hemicalide 1107 was also solved by synthesis.…”

Biological Activity of Recently Discovered Halogenated Marine Natural Products

“… Structures of placotylenes A ( 624 ) and B ( 625 ) from the sponge Placospongia sp. [ 218 ] and chalinulasterol ( 626 ) from the sponge Chalinula molitba [ 219 ]. …”

“…Placotylene A inhibits osteoclast differentiation of bone marrow-derived macrophages, perhaps by decreasing the expression of RANKL (receptor activator of nuclear factor-κB ligand). This marine polyacetylene could represent a lead compound for osteoporosis treatment [ 218 ]. The Caribbean sponge Chalinula molitba has afforded the novel chlorinated sterol disulfate, chalinulasterol ( 626 ) ( Figure 120 ).…”