nogalamycin and the duplex sequence dTpA (Brown et al., 1984), where it has been suggested that the sugar group at each end of the drug molecule (Fig. 2) sterically blocks the free movement of the chromophore in and out of the intercalation site. The intercalation process in solution has been extensively studied most often with reference to random-sequence DNA, and rather more rarely with respe...

XR5944, a deoxyribonucleic acid (DNA) bis-intercalator with potent anticancer activity, can bind the estrogen response element (ERE) sequence to inhibit estrogen receptor-α activities. This novel mechanism of action may be useful for overcoming drug resistance to currently available antiestrogen treatments, all of which target the hormone-receptor complex. Here we report the nuclear magnetic re...

Flavonoids and other polyphenolic compounds have been shown to inhibit human topoisomerase IB (topo I) through both inhibition of relaxation activity and through stabilization of the cleavable complex (poisoning). Some flavonoids have also been shown to intercalate DNA, and an association of topoisomerase inhibition with intercalation has been noted. We surveyed 34 polyphenolic compounds, prima...

A redox active and electrochemiluminescent (ECL) threading bis-intercalator, consisting of two N,N'-bis(3-propyl-imidazole)-1,4,5,8-naphthalene diimides (PIND) linked by a Ru(dmbpy)2(2+) (dmbpy = 4,4'-dimethyl-2,2'-bipyridine) complex (PIND-Ru-PIND), was synthesized for the first time. Its optical, electrochemical, and ECL properties were studied. UV-vis spectrophotometric measurements indicate...

Small molecules that bind to DNA are extremely useful as biochemical tools for the visualization of DNA both in vitro and inside the cell. Additionally, the clinical significance of DNA-binding compounds can hardly be overstated, as many anticancer regimens include a compound that binds to and/or modifies DNA. Although many of the important DNA-binding anticancer drugs were discovered in phenot...

Atomic force microscopy (AFM) has been used to examine perturbations in the tertiary structure of DNA induced by the binding of ditercalinium, a DNA bis-intercalator with strong anti-tumour properties. We report AFM images of plasmid DNA of both circular and linearised forms showing a difference in the formation of supercoils and plectonemic coils caused at least in part by alterations in the s...

Conjugation of an anthracycline to a triplex-forming oligonucleotide (TFO) allows delivery of this drug to a specific DNA site, preserving the intercalation geometry of this class of anticancer agents. Conjugate 11, in which the TFO is linked via a hexamethylene bridge to the O-4 on the D ring of the anthraquinone moiety, affords the most stable triple helix, through intercalation of the planar...

Quinoxaline antibiotics intercalate dsDNA and exhibit antitumor properties. However, they are difficult to synthesize and their structural complexity impedes a clear mechanistic understanding of DNA binding. Therefore design and synthesis of minimal-intercalators, using only part of the antibiotic scaffold so as to retain the key DNA-binding property, is extremely important. Reported is a uniqu...

The diverse anticancer utility of cisplatin has stimulated significant interest in the development of additional platinum-based therapies, resulting in several analogues receiving clinical approval worldwide. However, due to structural and mechanistic similarities, the effectiveness of platinum-based therapies is countered by severe side-effects, narrow spectrum of activity and the development ...