Molecular modeling study of interaction of anthracenedione class of drug mitoxantrone and its analogs with DNA tetrameric sequences.

Numbers of drugs are being synthesized every year to meet the target of safe and disease-free society. Presently molecular modeling technique is used to unfold the mechanism of action of drugs alone or in conjunction with experimental methodologies. There are a number of drugs which are successfully developed using this methodology. Mitoxantrone (MTX) - 1, 4-dihydroxy-5, 8-bis {[2-(2-hydroxyethyl) amino] amino}-9, 10-anthracenedione is marketed under the name Novantrone, an anticancer drug used in chemotherapy. Its important analog ametantrone and various other analogs differ from one another in the position of side chain or functionalities on the chromophore eventually exhibit varied biological activities. DNA binding is an important phenomenon for anticancer activity of these drugs. In order to understand the interactions of the drug molecules with its receptor site, at atomic level, we have carried out computer simulations of drug and DNA alone and also in complex mode in water as a medium. All the simulations are being carried out using molecular operating environment (MOE) and X3DNA software tools on SUN SOLARIS platform. Interaction energy of all the drug molecules with DNA is determined and compared. Also the structural changes in DNA and drug before and after complex formation are studied extensively.