Catalytic inhibitors of DNA topoisomerase II.

Abstract

Catalytic inhibitors of mammalian DNA topoisomerase II have been found recently in natural and synthetic compounds. These compounds target the enzyme within the cell and inhibit various genetic processes involving the enzyme, such as DNA replication and chromosome dynamics, and thus proved to be good probes for the functional analyses of the enzyme in a variety of eukaryotes from yeast to mammals. Catalytic inhibitors were shown to be antagonists against topoisomerase II poisons. Thus bis(2,6-dioxopiperazines) have a potential to overcome cardiac toxicity caused by potent antitumor anthracycline antibiotics such as doxorubicin and daunorubicin. ICRF-187, a (+)-enantiomer of racemic ICRF-159, has been used in clinics in European countries as cardioprotector. Furthermore, bis(2,6-dioxopiperazines) enhance the efficacy of topoisomerase II poisons by reducing their side effects in preclinical and clinical settings. Bis(2,6-dioxopiperazines) per se among others have antitumor activity, and one of their derivatives, MST-16 or Sobuzoxane, bis(N1-isobutyloxycarbonyloxymethyl-2, 6-dioxopiperazine), has been developed in Japan as an anticancer drug used for malignant lymphomas and adult T-cell leukemia in clinics.

• Authors: T Andoh, R Ishida
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1400 Issue 1-3 Pg. 155-71 (Oct 01 1998) ISSN: 0006-3002 [Print] Netherlands
• PMID: 9748552 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antineoplastic Agents
• Enzyme Inhibitors
• Intercalating Agents
• Piperazines
• Topoisomerase II Inhibitors

Topics

• Antineoplastic Agents (chemistry, pharmacology)
• Catalysis
• Enzyme Inhibitors (chemistry, therapeutic use)
• Humans
• Intercalating Agents (chemistry, therapeutic use)
• Molecular Structure
• Piperazines (chemistry, therapeutic use)
• Topoisomerase II Inhibitors