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ID: ALA1143443

Journal: Bioorg Med Chem Lett

Title: Discovery of (naphthalen-4-yl)(phenyl)methanones and N-methyl-N-phenylnaphthalen-1-amines as new apoptosis inducers using a cell- and caspase-based HTS assay.

Authors: Jiang S, Crogan-Grundy C, Drewe J, Tseng B, Cai SX.

Abstract: We report the discovery of a series of (naphthalen-4-yl)(phenyl)methanones as potent inducers of apoptosis using our proprietary cell- and caspase-based ASAP HTS assay. Through SAR studies, a group of N-methyl-N-phenylnaphthalen-1-amines also were identified as potent inducers of apoptosis. (1-(Dimethylamino)naphthalen-4-yl)(4-(dimethylamino)phenyl)methanone (2a), one of the most potent analogs, had EC(50) values of 37, 49 and 44nM in T47D, HCT116 and SNU398 cells, respectively. Compound 2a also was highly active in a growth inhibition assay with an GI(50) value of 34nM in T47D cells. Functionally, compound 2a arrested HCT116 cells in G(2)/M followed by induction of apoptosis and inhibited tubulin polymerization.

CiteXplore: 18849165

DOI: 10.1016/j.bmcl.2008.09.088