Xanthocidin derivatives as topoisomerase IIα enzymatic inhibitors.
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.
Department of Molecular Biology, Daiichi University of Pharmacy.
Shuso
S
Takeda
Kentaro
K
Yaji
Kenji
K
Matsumoto
Toshiaki
T
Amamoto
Mitsuru
M
Shindo
Hironori
H
Aramaki
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001688:Biological Products / Q000494:pharmacology*; D003517:Cyclopentanes / Q000494:pharmacology*; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D015394:Molecular Structure; D013302:Streptomyces / Q000737:chemistry*; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D001688:Biological Products; D003517:Cyclopentanes; D004268:DNA-Binding Proteins; D059005:Topoisomerase II Inhibitors; D004250:DNA Topoisomerases, Type II