DNA interaction with antitumoral molecules: a study by UV- spectroscopy, circular dichroism and docking calculations

In our recent interest on drug design and development of molecules with potential antitumoral activity, we have synthesized a series of new compounds by an efficient regioselective multi-component reaction. In National Cancer Institute (NCI-USA) assays, one of them has shown a potent and selective in vitro inhibition against melanoma cell line and it was promoted for in vivo investigations which are still in progress in National Institute of Health (NIH-USA). We report here on the interactions with natural DNA of these molecules and mitoxantrone, a chemotherapic drug in clinical use with a mechanism of action involving DNA intercalation. UV-visible spectroscopic analysis of DNA-complexes has been used to evaluate the binding constants, whereas informations on the stability of complexes were obtained by thermal denaturation experiments. A complementary approach has been investigated by circular dichroism (CD), able to establish the position and orientation of each ligand in DNA binding sites. Molecular docking computed for the ligand molecules with a double-strand oligonucleotide taken as a suitable model of natural DNA gave results in agreement with the experimental data and antitumoral activity.