A comprehensive review of topoisomerase inhibitors as anticancer agents in the past decade

The topoisomerase enzymes play an important role in DNA metabolism, and searching for enzyme inhibitors is an important target in the search for new anticancer drugs. Discovery of new anticancer chemotherapeutical capable of inhibiting topoisomerase enzymes is highlighted in anticancer research. Therefore, biologists, organic chemists and medicinal chemists all around the world have been identifying, designing, synthesizing and evaluating a variety of novel bioactive molecules targeting topoisomerase. This review summarizes types of topoisomerase inhibitors in the past decade, and divides them into nine classes by structural characteristics, including N-heterocycles compounds, quinone derivatives, flavonoids derivatives, coumarin derivatives, lignan derivatives, polyphenol derivatives, diterpenes derivatives, fatty acids derivatives, and metal complexes. Then we discussed the application prospect and development of these anticancer compounds, as well as concluded parts of their structural-activity relationships. We believe this review would be invaluable in helping to further search potential topoisomerase inhibition as antitumor agent in clinical usage. [Display omitted] •Topoisomerase inhibitors were primarily classified into nine structural classes.•Some exhibited exciting biological results better than the first line treatments.•Topo IIα inhibitors are more favorable than topo IIβ, but still with toxic to normal cells.•The mechanism of action needs further research.•The selectivity on the target and the in vivo tests should be focused on.