Bisdioxopiperazines

As mentioned in Section 3 of Chapter 4, this class of drugs were introduced as chelating agents, since they behave as pro-drugs to EDTA amides, and are useful as cardioprotectors when associated with anthracyclines. They have subsequently been shown to inhibit topoisomerase II at a point upstream to the formation of the cleavable DNA-enzyme complex by stabilizing the closed-clamp form of topoisomerase II as a post-passage complex. This is achieved by inhibiting the ATPase activity of the enzyme after interaction with its N-terminal domain. The main bis(dioxopiperazines)79 are shown below.

Compound

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