DNA constitutes a powerful target for chemotherapeutic intervention in human cancers, particularly for those where high proliferation rates of tumor cell types have resulted in sensitivity to drugs, which block replication and transcription of their DNA. Molecular detection of particular DNA sites by small molecules is an essential dilemma in drug design. Polycyclic heterocycles having a planar structure can be efficient pharmacophore moieties for DNA-interactive drugs because they can insert between the stacked base paired oligonucleotides or interact with grooves. Despite DNA being a significant target for numerous drugs, most of the docking programs are validated only for proteins and their ligands. In this paper, AutoDock 4.0 was used to perform self-dockings and cross dockings between seven DNA targets and five ligands belonging to 1,2-Phenylenediamine Schiff's base derivatives. AutoDock is able to correctly recognize main DNA binding modes. The obtained docking results are in absolute agreement with experimental data from the literature. In conclusion, our data that computational approaches on synthesized proposed ligands will contribute to select the most promising candidates as DNA-interactive drugs that have antitumor activity.