MOLECULAR MODELING - 9-ANILINEACRIDINE AN D ITS DNA INTERCALATION

Recently, drug focused molecular modeling studies have revealed to be a useful option for research with good results for the industry. In th is work, 9-anilineacridine, the most active compound among a group of molecules of known antimalarial and antitumour activities, was conside red to study a key step of the DNA topoisomerase II inhibition mechani sm, by means of simulating the intercalation of this drug in the DNA. Molecular modeling study was addressed to the insertion of the drug in to isolated DNA fragments constituted by different combinations of fou r nitrogenated bases. Energy and conformational parameters showed a be tter drug interaction for the CG/CG base pairs in agreement with exper imental data for other drug families. In addition, the insertion of th e drug into a major DNA fragment was studied focusing specifically to the CG/CG base pairs. Docking module of Biosym was used for that and e ach of the energy barriers generated during drug insertion were proper ly evaluated.