A Mini Review of Novel Topoisomerase II Inhibitors as Future Anticancer Agents

Abstract

Several reviews of inhibitors of topoisomerase II have been published, covering research before 2018. Therefore, this review is focused primarily on more recent publications with relevant points from the earlier literature. Topoisomerase II is an established target for anticancer drugs, which are further subdivided into poisons and catalytic inhibitors. While most of the topoisomerase II-based drugs in clinical use are mostly topoisomerase II poisons, their mechanism of action has posed severe concern due to DNA damaging potential, including the development of multi-drug resistance. As a result, we are beginning to see a gradual paradigm shift towards non-DNA damaging agents, such as the lesser studied topoisomerase II catalytic inhibitors. In addition, this review describes some novel selective catalytic topoisomerase II inhibitors. The ultimate goal is to bring researchers up to speed by curating and delineating new scaffolds as the leads for the optimization and development of new potent, safe, and selective agents for the treatment of cancer.

Synthesis of Novel N-Heterocyclic Carbene-Ruthenium (II) Complexes, “Precious” Tools with Antibacterial, Anticancer and Antioxidant Properties

“…This classification depends on the different mechanism of action of these two enzymes. hTopo I is able to break one strand of the double helix, regulating the levels of DNA supercoiling, while hTopo II breaks both strands [ 39 ]. Topoisomerases have assumed primary importance in oncological research since tumor tissues present a higher concentration of these enzymes, thus finding new agents able to specifically target topoisomerases is an important goal that could be exploited for anticancer therapeutic purposes [ 40 , 41 ].…”

Novel 2-substituted-quinoxaline analogs with potential antiproliferative activity against breast cancer: insights into cell cycle arrest, topoisomerase II, and EGFR activity

“…Two isoforms of topoisomerase II, topo II and topo II, have been identified. 81 The N-terminal domain of topoisomerase is the DNA-binding region, which finds and binds to target sequences of DNA. 82 The central catalytic domain is the enzyme's active site, where cleavage and re-ligation processes occur.…”

Metabolomic Profiling and Cytotoxic Activity of Launaea nudicaulis: Molecular Docking with Topoisomerases

“…The topoisomerase enzymes type I and type II are important in DNA metabolism, as these enzymes are responsible for adjustment of DNA supercoils which is vital element in transcription and replication cellular process. Both enzymes had been recognized as clinically significant targets for chemotherapy in cancer treatment through their inhibition (Okoro and Fatoki 2022). During the last 30 years, enzyme inhibitors with diverse structures have been established using drug screening and molecular simulation programs.…”