Background: Targeting the DNA topoisomerase II enzyme (topo II) is a promising anticancer
treatment approach. TopoII controls and modifies the topological states of DNA and plays key roles in
DNA replication, transcription, and chromosome segregation. The DNA binding and cleavage domain is
one of the active sites of this enzyme. It is known that topoisomerase inhibitors, also known as topoisomerase
poisons, bind to the transient enzyme-DNA complex and inhibit the religation of DNA, generating
single- and double-stranded breaks that harm the integrity of the genome. This ultimately leads to
the accumulation of DNA strand breaks and cell death.
Methods: Our previously synthesized benzazole derivatives were tested for their eukaryotic DNA topoisomerase
II inhibitory activity in a cell-free system. Their interactions with the enzyme were studied by
carrying out molecular docking studies using and comparing two different docking programs.
Results: The results of the docking studies clarified binding modes of these compounds to the topoisomerase
Conclusion: This study also provides guidelines to design novel and more potent antitumor agents functioning
as human topoisomerase II enzyme inhibitors.