Topoisomerase inhibitor

Topoisomerase inhibitors are chemical compounds that block the action of topoisomerases, which are broken into two broad subtypes: type I topoisomerases (TopI) and type II topoisomerases (TopII).[1][2][3] Topoisomerase plays important roles in cellular reproduction and DNA organization, as they mediate the cleavage of single and double stranded DNA to relax supercoils, untangle catenanes, and condense chromosomes in eukaryotic cells.[1][2][3] Topoisomerase inhibitors influence these essential cellular processes. Some topoisomerase inhibitors prevent topoisomerases from performing DNA strand breaks while others, deemed topoisomerase poisons, associate with topoisomerase-DNA complexes and prevent the re-ligation step of the topoisomerase mechanism.[3] These topoisomerase-DNA-inhibitor complexes are cytotoxic agents, as the un-repaired single- and double stranded DNA breaks they cause can lead to apoptosis and cell death.[2][3] Because of this ability to induce apoptosis, topoisomerase inhibitors have gained interest as therapeutics against infectious and cancerous cells.

  1. ^ a b Cooper GM (2019). The Cell: A Molecular Approach Eighth Edition. Oxford University Press. p. 222. ISBN 9781605357072.
  2. ^ a b c Nelson DL, Cox MM (2017). Lehninger Principles of Biochemistry Seventh Edition. W. H. Freeman and Company. pp. 963–971. ISBN 9781464126116.
  3. ^ a b c d Delgado JL, Hsieh CM, Chan NL, Hiasa H (2018-01-31). "Topoisomerases as anticancer targets". Biochemical Journal. 475 (2): 373–398. doi:10.1042/BCJ20160583. ISSN 0264-6021. PMC 6110615. PMID 29363591.