Synthesis and cytotoxic activity of N,N-bis-(3-[N-(4-chlorobenzo[g]-phthalazin-1-yl)]aminopropyl)-N-methylamine: a new potential DNA bisintercalator.

The synthesis of a new series of mono- and dinuclear 1-alkylamino-4-chlorobenzo[g]phthalazine derivatives 7–10 containing flexible polyaminic chains is reported. It has been achieved by the reaction of 1,4-dichlorobenzo[g]phthalazine with the corresponding polyamines. In vitro antitumoral activity against HT-29 human colon carcinoma cells was evaluated and showed best results for compound 10, in which two heteroaromatic units are linked by a N-methylsubstituted polyaminic chain. Molecular modelling of the complexes of 9 and 10 with DNA strongly suggests the possibility of bisintercalation, and also that the N-methyl group of 10 plays an important role in the formation of a specially stable DNA complex.