Synthesis of 7-oxo-7H-naphtho[1,2,3-de]quinoline derivatives as potential anticancer agents active on multidrug resistant cell lines.

Following our earlier finding that tetracyclic anthraquinone analogs with a fused pyridone ring exhibit cytotoxic activity toward multidrug resistant tumor cells, a series of new potential antitumor agents, 7-oxo-7H-naphtho[1,2,3-de]quinoline derivatives (3, 6-8, 10-12, 14, 15, and 18), bearing one or two basic side chains and various substituents at the pyridone ring, have been synthesized. The compounds have been obtained from 1-amino-4-chloroanthraquinone or 1-aminoanthraquinone by cyclization with diethyl malonate and the subsequent reactions of the key intermediates 2, 4, and 17. The compounds exhibited cytotoxic activity toward sensitive human leukemia cell line HL-60 and against its resistant sublines HL-60/VINC (MDR1 type) and HL-60/DX (MRP1 type).

2,7-Dihydro-3H-pyridazino[5,4,3-kl]acridin-3-one derivatives, novel type of cytotoxic agents active on multidrug-resistant cell lines. Synthesis and biological evaluation.

We have earlier postulated that the presence of a pyridazone ring fused with an anthracenedione moiety resulted in the analog's ability to overcome multidrug resistance of tumor cells [J. Med. Chem.

The activity of latent benzoperimidine esters to inhibit P-glycoprotein and multidrug resistance-associated protein 1 dependent efflux of pirarubicin from several lines of multidrug resistant tumor cells.

Multidrug resistance of tumor cells is associated with the presence of membrane proteins responsible for the cytostatics export. Recently, we have synthesized a new family of benzoperimidines causing the futile cycle of MDR pumps. In this study, biological data for benzoperimidine esters are presented for selected cell lines: sensitive (HL-60, GLC4, K562), P-gp resistant (HL-60/VINC, K562/DX), MRP1 resistant (HL-60/DX) and MRP1/LRP resistant (GLC4/DX).

Synthesis and biological evaluation of 2,7-Dihydro-3H-dibenzo[de,h]cinnoline-3,7-dione derivatives, a novel group of anticancer agents active on a multidrug resistant cell line.

A series of anthrapyridazone derivatives with one or two basic side chains at various positions in the tetracyclic chromophore have been synthesized. The key intermediates in the synthesis are 2,7-dihydro-3H-dibenzo[de,h]cinnoline-3,7-diones 1, 12 and 15 monosubstituted at position 2 (4d, 16a-e), or 6 (2a-f) or disubstituted at positions 2 and 6 (4a-c) or 2 and 8 (17a-e) with appropriate alkylaminoalkylamines. All analogues showed in vitro cytotoxic activity against murine leukemia (L1210) and human leukemia (K562) cell lines.

Effect of modification of 6-[(aminoalkyl)amino]-7H-benzo[e]-perimidin-7-ones on their cytotoxic activity toward sensitive and multidrug resistant tumor cell lines. Synthesis and biological evaluation.

Benzoperimidines, a novel group of antitumor anthracenedione analogues, are of interest due to their ability to overcome multidrug resistance of tumor cells (Stefańska, B., Dzieduszycka, M., Bontemps-Gracz, M.