Strongylophorine-26, an inhibitor of cancer cell Invasion: SAR revealed by synthesis of analogues.
The absolute configuration of strongylophorine-26 (1) was determined to be 4S, 5R, 8R, 9S, 10S, 13S, 14S by single-crystal X-ray diffraction analysis of the derivative 7 prepared from the co-occurring metabolite strongylophorine-8 (4) and chemical interconversion to the bislactone 8. Synthetic analogues (+)- and (-)-3 have been prepared in order to explore the structure-activity relationship for the anti-invasion pharmacophore of stronglylophorine-26. These studies revealed the unanticipated importance of the A ring lactone moiety for the anti-invasion activity of 1.
Warabi
Kaoru
K
Department of Chemistry, University of British Columbia, Vancouver, B.C. V6T 1Z1, Canada.
Patrick
Brian O
BO
Austin
Pamela
P
Roskelley
Calvin D
CD
Roberge
Michel
M
Andersen
Raymond J
RJ
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004224:Diterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
D000970:Antineoplastic Agents; D004224:Diterpenes; C491871:strongylophorine-26