From groove binding to intercalation: unravelling the weak interactions and other factors modulating the modes of interaction between methylated phenanthroline-based drugs and duplex DNA.

Several antitumor drugs base their cytotoxicity on their capacity to intercalate between base pairs of DNA. Nevertheless, it has been established that the mechanism of intercalation of drugs in DNA starts with the prior groove binding mode of interaction of the drug with DNA. Sometimes, for some kind of flat small molecules, groove binding does not produce any cytotoxic effect and the fast transition of such flat small molecules to the cytotoxic intercalation mode is desirable.

Unraveling the Modulation of the Activity in Drugs Based on Methylated Phenanthroline When Intercalating between DNA Base Pairs.

Phenanthroline derivatives intercalate between base pairs of DNA and produce cytotoxic effects against tumoral cells. Nevertheless, modulation of their efficiency by substitution remains unclear in bibliography. In this work, the effects of methylation of phenanthroline, in number and position, when it intercalates between guanine-cytosine base pairs (GC/CG), were studied with PM6-DH2 and DFT-D methods including dispersion corrections.