Acridine and imidazole were combined and synthesized 3,8-disubstituted-propyl-3H-imidazo[4,5-a]acridine-11-carbonitrile, as a new derivative. The interaction of this new compound with the topoisomerase enzyme was studied by molecular dynamics simulation. The 3,8-disubstituted-3H-imidazo[4,5-a]acridine-11-carbonitrile structure has been optimized by the density functional theory method. According to the results obtained from the molecular dynamics simulation, Arg364, Lys532, Asp533, Tyr537, Arg590, Cys630, Asn631, Gln633 and Adenine11 interact with the ligand by hydrophobic interactions and Arg488 and Adenine12 interact with the ligand by hydrogen bond interactions. Due to the fact that some of these residues, Arg488 and Arg590 are located in the enzyme active site, the new ligand appears to be inhibitory effect. Also, the calculation of the Harmonic Oscillator Model for Aromaticity (HOMA) index showed that the 5-membered ring of ligand and the 6-membered ring attached to the 5-membered ring had more reactivity with the enzyme. The contribution of charged residues in the binding free energy of the ligand is greater than the uncharged residues. Manuscript profile