Etoposide is effective as an anti-tumour drug by inhibiting eukaryotic DNA 
topoisomerase II via establishing a covalent complex with DNA. Unfortunately, 
its wide therapeutic application is often hindered by multidrug resistance 
(MDR), low water solubility and toxicity. In our previous study, new derivatives 
of benzoxazoles, benzimidazoles and related fused heterocyclic compounds, which 
exhibited significant eukaryotic DNA topoisomerase II inhibitory activity, were 
synthesized and exhibited better inhibitory activity compared with the drug 
etoposide itself. To expose the binding interactions between the eukaryotic 
topoisomerase II and the active heterocyclic compounds, docking studies were 
performed, using the software Discovery Studio 2.1, based on the crystal 
structure of the Topo IIA-bound G-segment DNA (PDB ID: 2RGR). The research was 
conducted on a selected set of 31 fused heterocyclic compounds with variation in 
structure and activity. The structural analyses indicate coordinate and hydrogen 
bonding interactions, van der Waals interactions and hydrophobic interactions 
between ligands and the protein, as Topo IIA-bound G-segment DNA are responsible 
for the preference of inhibition and potency. Collectively, the results 
demonstrate that the compounds 1a, 1c, 3b, 3c, 3e and 4a are significant 
anti-tumour drug candidates that should be further studied.