DNA intercalators as anticancer agents

Abstract

Cancer is one of the most prevailing disease conditions, which occurs due to uncontrolled cell division either due to natural mutation to the genes or due to changes induced by physical, chemical, or biological carcinogens. According to WHO, it is the second leading cause of death worldwide and has reported 10 million deaths in 2020. Hence, there arises the need for better chemotherapies and DNA intercalators are one such emerging therapy for cancer. DNA intercalating agents reversibly intercalate with the double‐helical structure of DNA by interacting with adjacent base pairs and disrupting the structure of DNA and thereby causing cell death. Here, we discuss the different classes of organo‐intercalators used in cancer therapy describing their anticancer and intercalation ability by different methods along with their structure–activity relationship and mechanism of action.

Synthetic Peptides: Promising Modalities for the Targeting of Disease‐Related Nucleic Acids

“…DNA in its double helix does not present ‘druggable’ binding pockets for small molecules. DNA‐targeted small molecules, indeed, usually have sequence agnostic unspecific affects, [8] ultimately leading to DNA damage and cell death [9] . An exceptional class of small molecules, the pyrrole‐imidazole polyamides, mainly discovered and investigated by Dervan et al., can target specific DNA sequences, via minor groove binding and base pair recognition [10] .…”

Sustained Delivery of Cu(II)-Based DNA Intercalators by Nanometer-Sized Cyclodextrin-Based Porous Polymers

“…DNA intercalation is a process where compounds with planar (hetero)­aromatic ring moieties insert between adjacent DNA base pairs perpendicularly to the helical axis. , While Watson–Crick base pairing is not perturbed by the intercalating ligands, other conformational changes in the DNA, such as partial unwinding, must occur to accommodate the intercalator . These structural changes have various functional repercussions, including the inhibition of DNA transcription and replication.…”

“…1,2 While Watson− Crick base pairing is not perturbed by the intercalating ligands, other conformational changes in the DNA, such as partial unwinding, must occur to accommodate the intercalator. 3 These structural changes have various functional repercussions, including the inhibition of DNA transcription and replication. Intercalators are thus one family of therapeutics used in chemotherapy to limit the propagation of cancer cells.…”

Indole Derived Anticancer Agents

“…Oxygen, nitrogen and sulfur are among the most common heteroatoms. Heterocyclic compounds are widely used in agrochemicals, pharmaceuticals and veterinary products [5,6] . Biaryl skeletons are ubiquitous in many natural products and pharmaceutical molecules, including the indole biaryl scaffold, which has been shown to possess a variety of potent biological properties [7,8] .…”

“…Heterocyclic compounds are widely used in agrochemicals, pharmaceuticals and veterinary products. [5,6] Biaryl skeletons are ubiquitous in many natural products and pharmaceutical molecules, including the indole biaryl scaffold, which has been shown to possess a variety of potent biological properties. [7,8] There are a variety of indole-based natural compounds, including alkaloids, hormones, antibiotics, vitamins, amino acids, dyes, hemoglobin and pigments.…”