Synthesis and biological evaluation of indeno[1,5]naphthyridines as topoisomerase I (TopI) inhibitors with antiproliferative activity.
Alonso C, Fuertes M, González M, Rubiales G, Tesauro C, Knudsen BR, Palacios F.
In an effort to establish new candidates with improved anticancer activity, we report here the synthesis of various series of 7H-indeno[2,1-c][1,5]-naphthyridines and novel 7H-indeno[2,1-c][1,5]-naphthyridine-7-ones and 7H-indeno[2,1-c][1,5]-naphthyridine-7-ols. Most of the products which were synthesized were able to inhibit Topoisomerase I activity. Moreover, in vitro testing demonstrated that a subset of the products exhibited a cytotoxic effect on cell lines derived from human breast cancer (BT 20), human lung adenocarcinoma (A 549), or human ovarian carcinoma (SKOV3).