Synthesis and antiproliferative activity of oxazinocarbazole and N,N-bis(carbazolylmethyl)amine derivatives.

The synthesis, structure elucidation and antitumoral activity of novel heterocyclic compounds containing a carbazole nucleus are reported. Oxazinocarbazoles were synthesized by application of the Mannich reaction to the corresponding hydroxylated derivatives leading to 41 new molecules. Their cytotoxic activity was evaluated against various human tumor cell lines including three leukemic cell lines: CEM and Jurkat (type T), Raji (type B); breast cancer cell line (MCF-7); colorectal cancer cell line (Caco-2). A primary screening at 100 microM allowed the selection of the 10 most active compounds, which showed an antiproliferative activity on all the cell lines. A dose-effect study between 12.5 and 100 microM sorted two compounds with a significant activity: 5t and 7e against leukemic cell lines CEM, Jurkat and Raji with IC50 values around 12 microM. Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.