Synthesis, Antitumor Cytotoxicity, and DNA-Binding of Novel N-5,2-Di(ω-aminoalkyl)-2,6-dihydropyrazolo[3,4,5-kl]acridine-5-carboxamides

A series of DNA-binding potential antitumor agents bearing a cationic carboxamide side chain attached in position peri to an electron-withdrawing atom, N-5,2-di(ω-aminoalkyl)-2,6-dihydropyrazolo[3,4,5-kl]acridine-5-carboxamides, has been prepared by reaction of the appropriate 1-chloro-9-oxo-9,10-dihydro-4-acridinecarboxamides with the suitable (ω-aminoalkyl)hydrazine. The noncovalent DNA-binding properties of these compounds have been examined using a fluorometric technique. In vitro cytotoxic potency of these derivatives toward the human colon adenocarcinoma cell line (HT29) is described and compared to that of reference drugs. Structure−activity relationships are discussed. Two highly DNA-affinic and potent cytotoxic compounds, 4m,o, have been identified as new leads in the antitumor strategies.