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)