Synthesis and an evaluation of the bioactivity of the C-glycoside of pseudopterosin A methyl ether.
The Suzuki-Miyaura cross-coupling protocol was applied to the synthesis of 1a, the C-glycoside analogue of PsA methyl ether. This marks the first construction of a C-glycoside for this class of marine natural products, thereby offering an opportunity to compare its bioactivity to the natural substances. Its activity profile resembled that of PsA (1) and PsA O-methyl ether (1b) when assayed for its anti-inflammatory activity and its ability to inhibit phagocytosis. We conclude that the intact structure is present when a pseudopterosin expresses its anti-inflammatory and phagocytosis inhibitory properties and that they are, therefore, not likely to be prodrugs. Results show that 1a is an effective binding agent toward the A2A and A3 adenosine receptors, displaying IC50 values of 20 and 10 microM, respectively.
Zhong
Wei
W
Department of Chemistry and Biochemistry, University of California, Santa Barbara, California 93106, USA.
Moya
Claudia
C
Jacobs
R S
RS
Little
R Daniel
RD
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D002460:Cell Line; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006027:Glycosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008738:Methyl Ethers / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D021261:Parasitic Sensitivity Tests; D010587:Phagocytosis / Q000187:drug effects; D043705:Receptor, Adenosine A2A / Q000187:drug effects; D043684:Receptor, Adenosine A3 / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D016808:Tetrahymena thermophila / Q000166:cytology / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D004224:Diterpenes; D006027:Glycosides; D008738:Methyl Ethers; D043705:Receptor, Adenosine A2A; D043684:Receptor, Adenosine A3; C049922:pseudopterosins