Topoisomerase inhibitor

Topoisomerase inhibitors are chemical compounds that block the action of topoisomerase (topoisomerase I and II), which are enzymes that control the changes in DNA structure by catalyzing the breaking and rejoining of the phosphodiester backbone of DNA strands during the normal cell cycle.

In recent years, topoisomerases have become popular targets for cancer chemotherapy treatments. It is thought that topoisomerase inhibitors block the ligation step of the cell cycle, generating single and double stranded breaks that harm the integrity of the genome. Introduction of these breaks subsequently leads to apoptosis and cell death.

Topoisomerase inhibitors can also function as antibacterial agents.Quinolones (including nalidixic acid and ciprofloxacin) have this function. Quinolones bind to these enzymes and prevent them from decatenation replicating DNA.

Topoisomerase inhibitors are often divided according to which type of enzyme it inhibits.

Numerous plant derived natural phenols (ex. EGCG,genistein, quercetin, resveratrol) possess strong topoisomerase inhibitory properties affecting both types of enzymes. They may express function of phytoalexins - compounds produced by plants to combat vermin and pests.

Use of topoisomerase inhibitors for antineoplastic treatments may lead to secondary neoplasms because of DNA damaging properties of the compounds. Also plant derived polyphenols shows signs of carcinogenity, especially in fetuses and neonates who do not detoxify the compounds sufficiently. An association between high intake of tea (containing polyphenols) during pregnancy and elevated risk of childhood malignant central nervous system (CNS) tumours has been found.

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