Synthesis of exotic polycycles such as cyclooctatrienes and fenestrenes with differential pro-apoptotic activities on human TRAIL-resistant metastatic cell lines.
New cyclooctatrienes were prepared by semihydrogenation of trienynes followed by 8π electrocyclization. Cyclooctatrienes and original fenestrenes previously reported were tested for their pro-apoptotic activities on two human cancer cell lines (THP-1 and SW620). Among the 20 new compounds tested, two compounds presented specific activities on the colon carcinomas TRAIL-resistant metastatic cell SW620, but a minor action on the monocytic leukemia THP-1 cell line. Six other compounds showed cell type specific activities: four induced apoptosis only in THP-1 cells and two only in SW620. Such differential pro-apoptotic activities suggest that these molecules could serve as potent pharmacological tools to study TRAIL associated cellular mechanisms.
Hulot
Catherine
C
UMR 7200 CNRS, Faculté de Pharmacie, Université de Strasbourg, 74 Route du Rhin, 67401 Illkirch, France.
Peluso
Jean
J
Blond
Gaëlle
G
Muller
Christian D
CD
Suffert
Jean
J
D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D006801:Humans; D011083:Polycyclic Compounds / Q000494:pharmacology*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000502:physiology*
D011083:Polycyclic Compounds; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human