Topoisomerase II inhibitors design: Early studies and new perspectives

The DNA topoisomerase enzymes are widely distributed throughout all spheres of life and are necessary for cell function. Numerous antibacterial and cancer chemotherapeutic drugs target the various topoisomerase enzymes because of their roles in maintaining DNA topology during DNA replication and transcription. Agents derived from natural products, like anthracyclines, epipodophyllotoxins and quinolones, have been widely used to treat a variety of cancers. A very active field of fundamental and clinical research is the selective targeting of topo-isomerase II enzymes for cancer treatment. This thematic review summarizes the recent advances in the anti-cancer activity of the most potent topoisomerase II inhibitors (anthracyclines, epipodophyllotoxins and fluoroquinolones) their modes of action, and structure-activity relationships (SARs) organized chronologically in the last ten years from 2013 to 2023. The review also highlights the mechanism of action and SARs of promising new topoisomerase II inhibitors.

Automated summary

DNA topoisomerase enzymes are essential for cell function and have been targeted by antibacterial and cancer chemotherapeutic drugs. This review focuses on the recent advances in the anti-cancer activity of topoisomerase II inhibitors (anthracyclines, epipodophyllotoxins, and fluoroquinolones), their modes of action, and structure-activity relationships (SARs). The review also highlights promising new topoisomerase II inhibitors and their mechanism of action and SARs.