FIGURE 7.13 Reactive species generated in etoposide metabolism.

Salvicine inhibits the catalytic activity of topoisomerase II with weak DNA cleavage action in contrast to the classic topoisomerase II poison etoposide. It stabilizes DNA strand breaks through interactions with the enzyme by trapping the DNA-topoisomerase II complex.75 Molecular modelling studies predicted that salvicine binds to the ATP pocket in the ATPase domain and superimposes on the phosphate and ribose groups, while competition with ATP was confirmed experimentally.76

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