Hernandez S. Mechanisms of interaction and competitive binding with DNA of aromatic antitumour drugs

The aim of the work was to study mechanisms of interaction of aromatic antitumour drugs of different secondary structures and its competitive binding with DNA. Methods of research are 1D and 2D NMR spectroscopy (500 MHz). The hetero-association of aromatic antitumour antibiotics Daunomycin, Nogalamycin, Mitoxantrone, Actinomycin D and bis-intercalator ethidium homodimer has been studied. The main contributors to the energy of association reactions were found to be a dispersive interactions of aromatic chromophores and hydrophobic interactions. It was also shown that the hetero-complexes of the antitumour antibiotics can be additionally stabilized by intermolecular H-bond. Bis-intercalator can form unfolded (U), folded (F) forms, partially-intercalated dimers (F2) and trimers (F3). Analysis of three-component equilibrium in Antibiotic-Antibiotic-DNA system has been made in terms of protector/interceptor action of one antibiotic on another for all combinations of antitumour antibiotics studied. It has been shown that the three-component mixture Antibiotic-Antibiotic-DNA allows for a directed regulation of the biological activity of a combination of aromatic antitumour drugs. Field of application - molecular and medical biophysics.