50 research outputs found
DNA Interactions of Monofunctional Organometallic Ruthenium(II) Antitumor Complexes in Cell-free Media
Modifications of natural DNA in a cell-free medium by antitumor monodentate Ru(II) arene
compounds of the general formula [(eta 6-arene)Ru(en)Cl]+ (arene ) biphenyl, dihydroanthracene,
tetrahydroanthracene, p-cymene, or benzene; en ) ethylenediamine) were studied by atomic absorption,
melting behavior, transcription mapping, circular and linear dichroism, plasmid unwinding, competitive
ethidium displacement, and differential pulse polarography. The results indicate that these complexes
bind preferentially to guanine residues in double-helical DNA. The data are consistent with DNA binding
of the complexes containing biphenyl, dihydroanthracene, or tetrahydroanthracene ligands that involves
combined coordination to G N7 and noncovalent, hydrophobic interactions between the arene ligand and
DNA, which may include arene intercalation and minor groove binding. In contrast, the single hydrocarbon
rings in the p-cymene and benzene ruthenium complexes cannot interact with double-helical DNA by
intercalation. Interestingly, the adducts of the complex containing p-cymene ligand, which has methyl
and isopropyl substituents, distort the conformation and thermally destabilize double-helical DNA distinctly
more than the adducts of the three multiring ruthenium arene compounds. It has been suggested that the
different character of conformational alterations induced in DNA, and the resulting thermal destabilization,
may affect differently further “downstream” effects of damaged DNA and consequently may result in
different biological effects of this new class of metal-based antitumor compounds. The results point to a
unique profile of DNA binding for Ru(II) arene compounds, suggesting that a search for new anticancer
compounds based on this class of complexes may also lead to an altered profile of biological activity in
comparison with that of metal-based antitumor drugs already used in the clinic or currently on clinical
trials