Antineoplastic DNA-Binding Compounds: Intercalating and Minor Groove Binding Drugs

Abstract

DNA intercalating and minor groove binding compounds are new weapons in the battle against malignant diseases. These antineoplastic agents target the DNA molecule and interfere with the cell cycle leading to rapidly proliferating cell death. They are mainly derivates of a naturally occurring organic compound derived from a microorganism or plant. Intercalators usually act as topoisomerase I and/or II poisons, while the mechanisms of DNA minor groove binders are a combination of several steps including topoisomerase poisoning. This paper gives an overview of some of the developed DNA intercalating and minor groove binding compounds, as well as an explanation of their chemical structures, origins, and application in chemotherapy.

Copper(II) complexes of coumarin-derived Schiff base ligands: Pro- or antioxidant activity in MCF-7 cells?

“…19,23,[38][39][40] The ability of the ligands and complexes to bind to DNA was assessed using a competitive ethidium bromide (Et + ) fluorescence displacement assay using CT-DNA (calf-thymus, ultrahigh purity) which allowed comparison with the known DNA intercalator actinomycin D and the DNA minor groove binder pentamidine. 36,37 None of the ligands showed any ability to interact with DNA and only complexes 6 and 7 showed reasonable ability to interact, though not as avidly as actinomycin D, (Table 6), (full data given in Supplementary Information) or indeed to related copper(II) square planar complexes previously published.…”

The 1,10-Phenanthroline Ligand Enhances the Antiproliferative Activity of DNA-Intercalating Thiourea-Pd(II) and -Pt(II) Complexes Against Cisplatin-Sensitive and -Resistant Human Ovarian Cancer Cell Lines

“…Therefore, our complexes bearing the phenanthroline moiety, in particular those with Pd(II), are likely powerful nucleic acid inhibitors. In particular, like the most clinically used DNA intercalating compounds [30], they may more strongly stabilize, lengthen, stiffen, and unwind the DNA double helix, thus concurring to the observed remarkable biological effect.…”

Dual Inhibitors Targeting DNA and Histone Deacetylases

“…DNA intercalators could intercalate and stack between the adjacent DNA base pairs, 14 which resulted in elongation of the DNA, 15 finally interrupting the replication, transcription, and DNA repair processes. 16 Topoisomerases (Topo) could combine with DNA to form a reversible covalent Topo-DNA complex and modulate DNA supercoiling. 17 Topo inhibitors could intercalate into DNA base pairs and maintain the structure of the DNA-enzyme cleavable complex.…”