Molecular Modeling of indeno [1,2-b] quinoline-9,11-diones as cytotoxic agents

Deoxyribonucleic acid (DNA) is an important molecular target for anti-cancer agents due to its involvement in gene expression and protein synthesis which are fundamental steps in cell division and growth. A number of antineoplastic agents interfere with DNA and hence disturb the cell cycle. Compounds including planar aromatic rings are privileged scaffolds in binding to the DNA. This characteristic is mainly arisen from the fact that such structural feature may be appropriate to insert between the base pairs of the DNA double helix and produce relatively stable non-covalent complexes. Besides π-π stacking interactions, binding to the DNA molecule might be intensified through H-bond interactions due to the presence of heterocyclic rings. In the present contribution, a series of experimentally validated cytotoxic indeno [1,2-b] quinoline-9,11-diones (1-12) and their aromatized analogues (13-21) developed in our group were subjected to docking and molecular dynamics simulations to elucidate their most probable binding modes with DNA.