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DNA Topoisomerases and Their Poisoning by Anticancer and Antibacterial Drugs
Open accessAbstract
DNA topoisomerases are the targets of important anticancer and antibacterial drugs. Camptothecins and novel noncamptothecins in clinical development (indenoisoquinolines and ARC-111) target eukaryotic type IB topoisomerases (Top1), whereas human type IIA topoisomerases (Top2alpha and Top2beta) are the targets of the widely used anticancer agents etoposide, anthracyclines (doxorubicin, daunorubicin), and mitoxantrone. Bacterial type II topoisomerases (gyrase and Topo IV) are the targets of quinolones and aminocoumarin antibiotics. This review focuses on the molecular and biochemical characteristics of topoisomerases and their inhibitors. We also discuss the common mechanism of action of topoisomerase poisons by interfacial inhibition and trapping of topoisomerase cleavage complexes.
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Tewey, K. M., Chen, G. L., Nelson, E. M., & Liu, L. F. (1984) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)47282-6 · Cited by 887 · cited 1×
“Inhibition of Top2 catalytic activity without trapping cleavage complexes is also observed for DNA intercalators at drug concentrations that alter DNA structure, thereby preventing Top2 from binding DNA (step 1 in Figure 5A) or from forming Top2cc (step 3) (Pommier et al., 1984; Tewey et al., 1984).”
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Metadata
- Authors
- Pommier, Y., Leo, E., Zhang, H., & Marchand, C.
- Venue
- Chemistry & Biology
- Publisher
- Elsevier BV
- Published
- 2010-05
- Volume
- 17
- Issue
- 5
- Pages
- 421-433
- ISSN
- 1074-5521 (ISSN-L)
- OpenAlex
- W2068577449
- Cited by
- 1,829
- References
- 1
- FWCI
- 29.30
- Type
- journal article
- Language
- en
- Open access
- hybrid
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