title: Heterofibrins: inhibitors of lipid droplet formation from a deep-water southern Australian marine sponge, Spongia (Heterofibria) sp.
abstract: 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
authors.affiliation: Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Queensland, 4072, Australia.
authors.forename: Angela A
authors.initials: AA
authors.lastname: Salim
authors.forename: James
authors.initials: J
authors.lastname: Rae
authors.forename: Frank
authors.initials: F
authors.lastname: Fontaine
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Conte
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Khalil
authors.forename: Sally
authors.initials: S
authors.lastname: Martin
authors.forename: Robert G
authors.initials: RG
authors.lastname: Parton
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Capon
mesh_terms: D000818:Animals; D001419:Bacteria / Q000187:drug effects; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D003593:Cytoplasm / Q000187:drug effects* / Q000378:metabolism*; D005227:Fatty Acids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005658:Fungi / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D011161:Porifera / Q000737:chemistry*
chemical_list: D005227:Fatty Acids