Synthesis and Antiproliferative Activity of Chlorinated Maprotiline Analogues

Abstract

A novel chlorinated tetracyclic compound 13 of the class ethanoanthracene as analogue of maprotiline was prepared via multistep syntheses. The tetracyclic key intermediate 5 with its [2.2.2] system was built nicely and economically in one-step via a Diels-Alder reaction between acrolein and 1,8-dichloroanthracene, followed by Wittig C-2 homologation. The synthesized chlorinated maprotiline analogues 6 , 7 and 13 as well intermediates 4 and 5 exerted antiproliferative activity in cancer cell lines A549 and HePG2 at low micromolar concentrations. In addition, the intermediates 4 and 5 were also had high activity against HCT cell line. Interestingly, the intermediate 4 was the most active against all cell lines studied.