DNA binding properties and evaluation of cytotoxic activity of 9,10-bis-N-substituted (aminomethyl)anthracenes

The results of DNA binding properties for four selected N-substituted 9,10-bis(aminomethyl)anthracenes are presented. DNA binding affinities were studied using UV-vis and fluorescence spectrophotometric titrations, CD spectroscopy, denaturation transition temperature (Tm) measurements and AM1 quantum chemical calculations. The results obtained indicate that the anthracene products intercalate into the stacked base pairs of DNA with binding constants, K, in the range 1.3-10.9 x 10(5)M(-1) and the binding site size in DNA-base pairs, n, extending over the range 2.4-4.6. Tm values increased in the presence of the anthryl probes, thereby reflecting an increased stability of the calf-thymus (CT) DNA double helix and rendering agreement with the spectrometric titration results. The synthesized compounds were tested against L1210 and HeLa tumor cell lines wherein the HeLa cells appeared to be more sensitive than the L1210 cells. 9,10-Bis{[2-(piperazin-1-yl)ethyl]aminomethyl}anthracene exhibited the highest activity of the tested compounds. Our findings were compared with those of a control drug bisantrene.