Synthetic pseudopterosin analogues: A novel class of antiinflammatory drug candidates.
The synthesis and in vivo anti-inflammatory activity of a series of pseudopterosin analogues are presented. Synthetic tricyclic catechol aglycons with different substitution patterns were monofucosylated or -xylosylated. Anti-inflammatory activity was conserved over a wide range of structural modifications. The most active synthetic compound 33 reduced phorbol myristate acetate (PMA)-induced inflammation in the mouse ear by 72% at 50 μg/ear. This corresponds to 80% of the activity of natural pseudopterosin A.
Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California at San Diego, La Jolla, 92093-0204, USA.
Felix
F
Flachsmann
Kurt
K
Schellhaas
Claudia E
CE
Moya
Robert S
RS
Jacobs
William
W
Fenical
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D002396:Catechols / Q000737:chemistry; D004224:Diterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D005697:Galactosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D006027:Glycosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D051379:Mice; D043803:Phenalenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity
C556291:4-hydroxy-3,3-dimethyl-2,3,7,8,9,9a-hexahydro-1H-phenalen-5-yl 6-deoxygalactopyranoside; D000893:Anti-Inflammatory Agents; D002396:Catechols; D004224:Diterpenes; D005697:Galactosides; D006027:Glycosides; D043803:Phenalenes; C049922:pseudopterosins; C034221:catechol; D013755:Tetradecanoylphorbol Acetate