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Oxygenated polyketides from Plakinastrella mamillaris as a new chemotype of PXR agonists
Carmen Festa1, Claudio D'Amore, Barbara Renga
1Department of Pharmacy, University of Naples "Federico II", via D. Montesano 49, Naples 80131, Italy. angela.zampella@unina.it
Abstract:
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 (1H and 13C, 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.
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