Oxygenated Polyketides from Plakinastrella mamillaris as a New Chemotype of PXR Agonists

Marine Drugs

Carmen Festa³  Claudio D𠆚more²  Barbara Renga²  Gianluigi Lauro¹  Simona De Marino³  Maria Valeria D𠆚uria³  Giuseppe Bifulco¹  Angela Zampella³ 

[1] Department of Pharmacy, University of Salerno, via Ponte don Melillo, Fisciano (SA) 84084, Italy; E-Mails:;Department of Clinical and Experimental Medicine, Faculty of Medicine, University of Perugia, via Gerardo Dottori 1, S. Andrea Delle Fratte, Perugia 06132, Italy; E-Mails:;Department of Pharmacy, University of Naples “Federico II”, via D. Montesano 49, Naples 80131, Italy; E-Mails:

关键词: marine sponge;    Plakinastrella mamillaris;    oxygenated polyketide;    nuclear receptors;    pregnane-X-receptor;    anti-inflammatory activity;   

DOI  :  10.3390/md11072314

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.