Synthesis and Antiproliferative Activity of Chlorinated Maprotiline Analogues

A novel chlorinated tetracyclic compound 13 of the class ethanoanthracene, as analogue of maprotiline, was prepared via multistep syntheses. The tetracyclic key intermediates 4 and 5 with its [2.2.2] system were built via a Diels-Alder reaction between acrolein and 1,8-dichloroanthracene.The synthesized chlorinated maprotiline analogues 6 , 7 and 13 as well intermediates 4 and 5 exerted antiproliferative activity against cancer cell lines A549 and HepG2 at low micromolar concentrations. In addition, the intermediates 4 and 5 exerted high antiproliferative activity against HCT cell line. Interestingly, the intermediate 4 was the most active against all treated cell lines.