%0 Journal Article %J Bioorg Med Chem Lett %D 2012 %T Design and synthesis of Pictet-Spengler condensation products that exhibit oncogenic-RAS synthetic lethality and induce non-apoptotic cell death. %A Skouta, Rachid %A Hayano, Miki %A Shimada, Kenichi %A Stockwell, Brent R. %K Antineoplastic Agents %K Carbolines %K Cell Death %K Cell Line, Tumor %K Cell Survival %K Drug Design %K Gene Expression Regulation, Neoplastic %K Genes, ras %K Humans %K Neoplasms %X A series of Pictet-Spengler condensation derivatives (tetrahydro-β-carbolines) was designed, synthesized and evaluated for lethality against a panel of seven cancer cell lines. Seven compounds (2a, 13, 20, 21, 27, 29 and 34) showed lethality in at least five cell lines. Among these, compound 27 showed a unique selectivity towards oncogenic-RAS expressing BJ-TERT/LT/ST/RAS(V12) tumor cells, compared to non-transformed BJ-TERT cells. Further investigation revealed that 27 induces cell death without activation of caspases. This represents a useful new probe of non-apoptotic cell death and oncogenic-RAS synthetic lethality. %B Bioorg Med Chem Lett %V 22 %P 5707-13 %8 2012 Sep 1 %G ENG %N 17 %1 http://www.ncbi.nlm.nih.gov/pubmed/22832321?dopt=Abstract %R 10.1016/j.bmcl.2012.06.077