pi-pi Molecular interactions between intercalating antitumor agents and caffeine

Many antitumor drugs function by intercalating into DNA and forming pi-pi molecular complexes. The drugs can also form these bonds with other planar aromatic structures such as the xanthine alkaloid caffeine, which may block the drug from intercalating into the DNA, thereby lowering the toxicity of the drug to the cancer cells. The IC 50 values of several known DNA intercalators were determined by testing for cytotoxicity on MCF-7 breast cancer cells both in the presence and absence of caffeine to test for attenuation in cytotoxicity of each drug. Computational molecular modeling studies involving several intercalating antitumor drugs with caffeine were also performed using the density functional theory and the recently developed M06 functional to discover the most probable configuration of the two interacting molecules determined by their interaction energies.