Recent advance in small organic molecules as intercalating agents: synthesis, activity and modelling

The interaction of small molecules with DNA plays an essential role in many biological processes. As DNAis often the target for majority of anticancer and antibiotic drugs, study about the interaction of drug andDNA has a key role in pharmacology. Moreover, understanding the interactions of small molecules withDNA is of prime significance in the rational design of more powerful and selective anticancer agents. Twoof the most important and promising targets in cancer chemotherapy include DNA alkylating agents andDNA intercalators. For these last the DNA recognition is a critical step in their anti-tumor action and theintercalation is not only one kind of the interactions in DNA recognition but also a pivotal step of severalclinically used anti-tumor drugs such as anthracyclines, acridines and anthraquinones. To push clinicalcancer therapy, the discovery of new DNA intercalators has been considered a practical approach and anumber of intercalators have been recently reported. The intercalative binding properties of such moleculescan also be harnessed as diagnostic probes for DNA structure in addition to DNA-directedtherapeutics.Moreover, the problem of intercalation site formation in the undistorted B-DNA of different length andsequence is matter of tremendous importance in molecular modeling studies and, nowadays, threemodels of DNA intercalation targets have been proposed that account for the binding features ofintercalators. Finally, despite DNA being an important target for several drugs, most of the dockingprograms are validated only for proteins and their ligands. Therefore, a default protocol to identify DNAbinding modes which uses a modified canonical DNA as receptor is needed.