Since the discovery of DNA intercalating agents (by Lerman, 1961), a growing number of organic, inorganic, and metallic compounds have been developed to treat life-threatening microbial infections and cancers. Fused-heterocycles are amongst the most important group of compounds that have the ability to interact with DNA. DNA intercalators possess a planar aromatic ring structure that inserts itself between the base pairs of nucleic acids. Once inserted, the aromatic structure makes van der Waals interactions and hydrogen-bonding interactions with the base pairs. The DNA intercalator may also contain an ionizable group that can form ionic interactions with the negatively charged phosphate backbone. After the intercalation, other cellular processes could take place, leading ultimately to cell death. The heterocyclic nucleus present in the DNA intercalators can be considered as a pharmacophore that plays an instrumental role in dictating the affinity and selectivity exhibited by these compounds. In this work, we have carried out a revision of small organic molecules that bind to the DNA molecule via intercalation and cleaving and exert their antitumor activity. A general overview of the most recent results in this area, paying particular attention to compounds that are currently under clinical trials, is provided. Advancement in spectroscopic techniques studying DNA interaction can be examined in-depth, yielding important information on structure-activity relationships. In this comprehensive review, we have focused on the introduction to fused heterocyclic agents with DNA interacting features, from medicinal point of view. The structure-activity relationships points, cytotoxicity data, and binding data and future perspectives of medicinal compounds have been discussed in detail.

Docking studies are proved to be an essential tool that facilitates the structural diversity of natural products to be harnessed in an organized manner. In this study, pyridoacridines containing natural anticancer pigments were subjected to docking studies using Glide (Schrodinger). Investigations were carried out to find out the potential molecular targets for these selected pigments. The docking was carried out on different cancer macromolecules involved in different cell cycle pathways, that is, CDK-2, CDK-6, Bcl-2, VEGFR-2, IGF-1R kinase, and G-Quadruplexes. CDK-6 was found to be the most suitable anticancer target for the pyridoacridines. In addition, effectiveness of the study was further evaluated by performing docking of known inhibitors against their respective selected macromolecules. However, the results are preliminary and experimental evaluation will be carried out in near future.

Natural products are increasingly being considered "critical and important" in drug discovery paradigms as a number of them such as camptothecin, penicillin, and vincristine serve as "lead molecules" for the discovery of potent compounds of therapeutic interests namely irinotecan, penicillin G, vinblastine respectively. Derived compounds of pharmacological interests displayed a wide variety of activity viz. anticancer, anti-inflammatory, antimicrobial, anti-protozoal, etc.; when modifications or derivatizations are performed on a parent moiety representing the corresponding derivatives. Pyridoacridine is such a moiety which forms the basic structure of numerous medicinally important natural products such as, but not limited to, amphimedine, ascididemin, eilatin, and sampangine. Interestingly, synthetic analogues of natural pyridoacridine exhibit diverse pharmacological activities and in view of these, natural pyridoacridines can be considered as "lead compounds". This review additionally provides a brief but critical account of inherent structure activity relationships among various subclasses of pyridoacridines. Furthermore, the current aspects and future prospects of natural pyridoacridines are detailed for further reference and consideration.