New antitumoral molecules and DNA interactions: a study by docking calculations supporting spectroscopic evidences and biological activities

In our recent activity on drug design and development of potential antitumoral agents having natural products and clinically-used drugs as templates, we synthesized a series of new molecules by an efficient procedure involving a multicomponent approach and microwave irradiation. The structure is characterized by a planar hetero-polycyclic unit that can insert between the stacked base paired oligonucleotides, and bearing suitable side chains able to further interactions with DNA. The compounds were tested for their in vitro citotoxicity by National Cancer Institute (NCI-USA) and one of them, showing a potent and selective inhibition against melanoma cells, was selected for in vivo assays by National Institute of Health (NIH-USA), where is currently under investigation. Later, these new molecules have been studied by spectroscopic techniques (temperature dependent UV-visible and circular dichroic analyses), with the aim of understanding the mechanism of action of the corresponding DNA/ligand systems. We report here the results from molecular docking calculations (by using the software package AutoDock) for DNA interactions with some of these molecules, having the drug mitoxantrone as a reference. The results allowed to estimate the interaction energies and geometries, pointing to a higher interaction as intercalator of DNA just with the molecule showing both the higher interaction by spectroscopic investigation and the most potent antitumoral activity