Abstract
Continuing our ongoing studies on cytotoxic substances, we report the synthesis and cytotoxic properties of a series of symmetric 1,5βdiaminoβ9,10βanthraquinones with potentially bioreducible groups. Symmetric amination of 1,5βdichloroβ9,10βanthraquinone with the appropriate primary amines in the presence of DMF furnished the structurally related aminoanthraquinone analogs 1β19. Their in vitro cytotoxic activity was evaluated using rat glioma C6 cells, human hepatoma G2 cells, and 2.2.15 cells. Several compounds exhibited very high antitumor activities in these assays. Compound 4 efficiently inhibited C6 cells, human hepatoma G2 cells, and 2.2.15 cells, as determined by means of the XTT colorimetric assay. The antiproliferative activity of 4 was markedly enhanced, reaching a potency comparable to those of the powerful anticancer agents mitoxantrone, adriamycin, and cisplatin. Biological evaluations and structure/activity relationships within this class of novel aminoanthraquinones are discussed.