Integrating molecular docking, DFT and CoMFA/CoMSIA approaches for a series of naphthoquinone fused cyclic α-aminophosphonates that act as novel topoisomerase II inhibitors.

Since they are potential topoisomerase II (Topo II) inhibitors, naphthoquinone fused cyclic α-aminophosphonates display anticancer activity. In order to explore the inhibitory mechanisms of these compounds, they were docked into the active site of Topo II structure, which allowed their probable binding modes to be predicted. Some meaningful results concerning their structure-activity relationships were obtained from density functional theory calculations. Models based on quantitative comparative molecular field analysis and comparative molecular similarity index analysis were derived for the steric, electrostatic, hydrophobic and H-bonding features of the compounds. The present study provides valuable results that enhance our understanding of the anticancer activities of these inhibitors and will aid the rational drug design of novel Topo II inhibitors in the future.