Darwinolide, a New Diterpene Scaffold That Inhibits Methicillin-Resistant Staphylococcus aureus Biofilm from the Antarctic Sponge Dendrilla membranosa

• Published in: Organic letters Vol. 18; no. 11; pp. 2596 - 2599
• Main Authors: von Salm, Jacqueline L, Witowski, Christopher G, Fleeman, Renee M, McClintock, James B, Amsler, Charles D, Shaw, Lindsey N, Baker, Bill J
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 03-06-2016
• Subjects: Animals; Antarctic Regions; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - isolation & purification; Anti-Bacterial Agents - pharmacology; Biofilms - drug effects; Cell Line; Dendrilla membranosa; Diterpenes - chemistry; Diterpenes - isolation & purification; Diterpenes - pharmacology; Inhibitory Concentration 50; Letter; Methicillin-Resistant Staphylococcus aureus - drug effects; Methicillin-Resistant Staphylococcus aureus - growth & development; Mice; Microbial Sensitivity Tests; Molecular Structure; Porifera - chemistry; Staphylococcus aureus
• ISSN: 1523-7060; 1523-7052
• DOI: 10.1021/acs.orglett.6b00979

A new rearranged spongian diterpene, darwinolide, has been isolated from the Antarctic Dendroceratid sponge Dendrilla membranosa. Characterized on the basis of spectroscopic and crystallographic analysis, the central seven-membered ring is hypothesized to originate from a ring-expansion of a spongian precursor. Darwinolide displays 4-fold selectivity against the biofilm phase of methicillin-resistant Staphylococcus aureus compared to the planktonic phase and may provide a scaffold for the development of therapeutics for this difficult to treat infection.