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
Salim
Angela A
AA
Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Queensland, 4072, Australia.
Rae
James
J
Fontaine
Frank
F
Conte
Melissa M
MM
Khalil
Zeinab
Z
Martin
Sally
S
Parton
Robert G
RG
Capon
Robert J
RJ
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*
D005227:Fatty Acids