A drug inhibits topoisomerase II by stabilising the cleavable complex (enzyme-DNA covalent intermediate), preventing strand religation. Which class of anticancer agent acts by this mechanism?
- A Camptothecins (irinotecan, topotecan), which poison topoisomerase II
- B Fluoroquinolones, which stabilise the topoisomerase II-DNA cleavable complex in mammalian cells
- C Acridine dyes, which intercalate into DNA and prevent topoisomerase II binding
- D Anthracyclines (doxorubicin) and etoposide, which are topoisomerase II poisons stabilising the cleavable complex ✓
Explanation
Topoisomerase II poisons include anthracyclines (doxorubicin, daunorubicin) and epipodophyllotoxins (etoposide, teniposide). They stabilise the transient covalent (cleavable) complex between topoisomerase II and the cut DNA strands, preventing religation and generating permanent double-strand breaks that trigger apoptosis. Camptothecins (irinotecan, topotecan) are topoisomerase I poisons, not topoisomerase II. Fluoroquinolones poison bacterial gyrase and topoisomerase IV (prokaryotic type II topoisomerases) with very low mammalian topoisomerase II affinity. Intercalation alone is different from poisoning.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
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