Heterofibrins: inhibitors of lipid droplet formation from a deep-water southern Australian marine sponge, Spongia (Heterofibria) sp.

A bioassay-guided search for inhibitors of lipid droplet formation in a deep-water southern Australian marine sponge, Spongia (Heterofibria) sp., yielded six new compounds, fatty acids heterofibrins A1 (1) and B1 (4), along with related monolactyl and dilactyl esters, heterofibrins A2 (2), B2 (5), A3 (3) and B3 (6). Heterofibrin structures were assigned on the basis of detailed spectroscopic analysis, with comparison to chiral synthetic model compounds. All heterofibrins possess a diyne-ene moiety, while the monolactyl and dilactyl moiety featured in selected heterofibrins is unprecedented in the natural products literature. SAR by co-metabolite studies on the heterofibrins confirmed them to be non-cytotoxic, with the carboxylic acids 1 and 4 inhibiting lipid droplet formation in A431 fibroblast cell lines. Such inhibitors have potential application in the management of obesity, diabetes and atherosclerosis

[1]  Yandi D. Liu,et al.  Dietary sandalwood seed oil modifies fatty acid composition of mouse adipose tissue, brain, and liver , 1997, Lipids.

[2]  Robert G. Parton,et al.  Opinion: Lipid droplets: a unified view of a dynamic organelle , 2006, Nature Reviews Molecular Cell Biology.

[3]  S. Arihara,et al.  Three novel C21 polyacetylenes from the marine sponge Callyspongia sp , 1997 .

[4]  S. Ōmura,et al.  Complete inhibition of mouse macrophage-derived foam cell formation by triacsin C. , 1999, Journal of biochemistry.

[5]  Butler,et al.  Isolation of xestosterol esters of brominated acetylenic fatty acids from the marine sponge xestospongia testudinaria , 1999, Journal of natural products.

[6]  E. Christ-Hazelhof,et al.  Naturally occurring conjugated octadecatrienoic acids are strong inhibitors of prostaglandin biosynthesis. , 1987, Prostaglandins.

[7]  S. Matsunaga,et al.  Antifungal Brominated C18 Acetylenic Acids from the Marine Sponge, Petrosia volcano Hoshino , 1993 .

[8]  S. Ōmura,et al.  Potential therapeutics for obesity and atherosclerosis: inhibitors of neutral lipid metabolism from microorganisms. , 2007, Pharmacology & therapeutics.

[9]  S. Matsunaga,et al.  H,K-ATPase inhibitors from the marine sponge siphonochalina truncata: Absolute configuration of siphonodiol and two related metabolites☆ , 1987 .

[10]  D. Youssef,et al.  Callyspongenols A-C, new cytotoxic C22-polyacetylenic alcohols from a red sea sponge, Callyspongia species. , 2003, Journal of natural products.

[11]  R. Parton,et al.  Caveolin, cholesterol, and lipid bodies. , 2005, Seminars in cell & developmental biology.

[12]  H. Hirota,et al.  Seven New Polyacetylene Derivatives, Showing Both Potent Metamorphosis-Inducing Activity in Ascidian Larvae and Antifouling Activity Against Barnacle Larvae, from the Marine Sponge Callyspongia truncata , 1997 .

[13]  D. Faulkner,et al.  Chlorinated acetylenes from the San Diego sponge Haliclona lunisimilis. , 2003, Journal of natural products.

[14]  T. Mosmann.  Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. , 1983, Journal of immunological methods.

[15]  D. Tucker,et al.  Further Acetylenic Acids from the Marine Sponge Xestospongia testudinaria , 1991 .

[16]  Y. Kashman,et al.  Brominated unsaturated acids from the marine sponge xestospongia sp. , 1987 .

[17]  J. R. Frank,et al.  Technological and economic potential of poly(lactic acid) and lactic acid derivatives , 1995 .

[18]  R. Barrow,et al.  Carduusynes (A-E) - Acetylenic Acids From a Great-Australian-Bight Marine Sponge Phakellia-Carduus , 1994 .

[19]  Anne E Carpenter,et al.  CellProfiler: image analysis software for identifying and quantifying cell phenotypes , 2006, Genome Biology.

[20]  A. Sinclair,et al.  Santalbic acid from quandong kernels and oil fed to rats affects kidney and liver P450. , 1999, Asia Pacific journal of clinical nutrition.

[21]  H. Arai,et al.  Scavenger receptor-mediated uptake and metabolism of lipid vesicles containing acidic phospholipids by mouse peritoneal macrophages. , 1990, The Journal of biological chemistry.

[22]  K. Iguchi,et al.  Nine acetylenic alcohols isolated from the Okinawan marine sponge of the genus Petrosia ( Strongylophora ) , 2007, Natural product research.