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.