Oxygenated Polyketides from Plakinastrella mamillaris as a New Chemotype of PXR Agonists
Further purification of the apolar extracts of the sponge Plakinastrella mamillaris, afforded a new oxygenated polyketide named gracilioether K, together with the previously isolated gracilioethers E-G and gracilioethers I and J. The structure of the new compound has been elucidated by extensive NMR (H-1 and C-13, COSY, HSQC, HMBC, and ROESY) and ESI-MS analysis. With the exception of gracilioether F, all compounds are endowed with potent pregnane-X-receptor (PXR) agonistic activity and therefore represent a new chemotype of potential anti-inflammatory leads. Docking calculations suggested theoretical binding modes of the identified compounds, compatible with an agonistic activity on hPXR, and clarified the molecular basis of their biological activities.
Festa Carmen, D'Amore Claudio, Renga Barbara, Lauro Gianluigi, de Marino Simona, D'Auria Maria Valeria, Bifulco Giuseppe, Zampella Angela, Fiorucci Stefano (2013). Oxygenated Polyketides from Plakinastrella mamillaris as a New Chemotype of PXR Agonists. Marine Drugs. 11 (7). 2314-2327. https://doi.org/10.3390/md11072314, https://archimer.ifremer.fr/doc/00217/32781/