Xanthocidin derivatives as topoisomerase IIα enzymatic inhibitors.

Abstract

Few studies have examined xanthocidin, a biotic isolated from Streptomyces xanthocidicus in 1966, because its supply is limited. Based on its chemical structure, xanthocidin has the potential to become a lead compound in the production of agrochemicals and anti-cancer drugs; however, it is unstable under both basic and acidic conditions. We recently established the total synthesis of xanthocidin using the FeCl3-mediated Nazarov reaction, and obtained two stable derivatives (#1 and #2). The results of the present study demonstrated that these derivatives exhibited the inhibitory activity of topoisomerase IIα, known as a molecular target for cancer chemotherapy, and this was attributed to the respective exo-methylene ketone group without DNA intercalation. The results obtained also suggest that these derivatives may have value as lead compounds in the synthesis of topoisomerase IIα inhibitors.

• Authors: Shuso Takeda, Kentaro Yaji, Kenji Matsumoto, Toshiaki Amamoto, Mitsuru Shindo, Hironori Aramaki
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 37 Issue 2 Pg. 331-4 ( 2014) ISSN: 1347-5215 [Electronic] Japan
• PMID: 24492731 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Antineoplastic Agents
• Biological Products
• Cyclopentanes
• DNA-Binding Proteins
• Topoisomerase II Inhibitors
• DNA Topoisomerases, Type II

Topics

• Antigens, Neoplasm
• Antineoplastic Agents (chemical synthesis, pharmacology)
• Biological Products (pharmacology)
• Cyclopentanes (pharmacology)
• DNA Topoisomerases, Type II
• DNA-Binding Proteins (antagonists & inhibitors)
• Humans
• Molecular Structure
• Streptomyces (chemistry)
• Topoisomerase II Inhibitors (chemical synthesis, pharmacology)