Maria Dzieduszycka

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. M., Borowski, E., Martelli, S., Supino, R., Pratesi, G., De Cesare, MA., Zunino, F., Kuśnierczyk, H., Radzikowski, Cz. J. Med. Chem. 1999, 42, 3494). Although the structural factor essential for exhibiting this desirable property is the presence in the molecule of a fused heterocyclic ring, the cytotoxicity against resistant cells is highly influenced by the nature and location of the substituents. A series of novel synthetic derivatives, comprising monohydroxylated benzoperimidines and 2-aminobenzoperimidines, allowed the establishment of an in vitro structure-activity relationship for a panel of leukemia sensitive, as well as P-gp dependent multidrug resistance (MDR) and multidrug resistance associated protein dependent resistance (MRP) resistant cell lines. The membrane affinity for the compounds has also been determined.

Synthesis, antileukemic evaluation and peroxidating ability of heterosubstituted anthracene-9,10-dione analogues: 5,8-[(aminoalkyl)amino]naphtho[2,3-d]thiazole-4,9-diones and 5,8-[(aminoalkyl)amino]naphtho[2,3-c] [1,2,5]thiadiazole-4,9-diones

Abstract The syntheses of a number of heterosubstituted ametantrone analogues, 5,8-bis[(aminoalkyl)amino]naphtho[2,3- d ]thiazole-4,9-diones and 5,8-bis[(aminoalkyl)amino]naphtho[2,3- c ] [1,2,5]thiadiazole-4,9-diones, have been performed. It was evidenced that this modification in the chromophore moiety has a negative effect on antileukemic activity. This modification also favors the affinity of the compounds toward NADH dehydrogenase and influences the redox potential.