Drugs acting on DNA topoisomerases: Recent advances and future perspectives

DNA-topoisomerases, a family of DNA-processing enzymes, represent the pharmacological target of major clinically useful chemotherapeutic agents. These drugs essentially act by trapping a topoisomerase-DNA cleavable complex, an intermediate in the enzyme s catalytic cycle. Research activity in this field continues to grow exponentially, resulting in a wealth of new information on the functional role and the biochemical and structural properties of the enzymes. In addition, the drug pharmacophores have been further characterized, along with their sequence preferences, and key interactions with the target macromolecules are being unveiled. This review will discuss the recent advances in elucidating the mode of action of DNA-topoisomerases and of topoisomerase-targeted anticancer agents.