STERIC HINDRANCE OF ANTITUMOR ANTHRACENEDIONES - MOLECULAR-DYNAMICS SIMULATION

It has been suggested that low efficiency in oxygen radicals formation observed for synthetic anti-tumor anthracenediones could result from their law affinity to NADH: dehydrogenase. Conformational analysis of side chains of ametantrone as well as mitoxantrone and its metabolite in hydrophobic environment, expected for catalytic center of NADH dehy drogenase, were simulated by molecular dynamics. Non-charged forms of studied compounds were analyzed. Characteristic conformations of side chains resulting from intramolecular hydrogen bonds were observed. Sta ble interchain hydrogen bonds placed side chains under or over the pla ne of anthraquinone ring system. Existance of hydrogen bonds between q uinone oxygen atoms and amino as well as hydroxyl groups of side chain s were also evidenced. Consequences of that conformational characteris tics for affinity of studied compounds to NADH dehydrogenase were disc ussed.