Topoisomerase inhibitors as therapeutic weapons

DNA topoisomerases (topos), which solve topological problems associated with various DNA transactions, are the targets of many therapeutic agents. Various topo inhibitors, especially the so-called topo-poisons, are drugs presently used in cancer treatment protocols. However, tumour resistance, as well as normal and non-specific tissue cytotoxicity are limitations for the successful development of these drugs as one of the primary therapeutic agents for the treatment of tumours. Major progress has been attained in recent years in the understanding of the structures of these enzymes and their main cellular functions, hopefully providing new opportunities for pharmacological interventions. Recently, new leads and derivatives of known structures have been reported and they are discussed here, highlighting the challenges to find innovative and more effective drugs. Moreover, the authors review novel and diverse approaches relevant to the development of new topo-related therapeutics other than cancer. This brie...