These researchers have cleverly identified a way to synthesize derivatives of an unstable compound group with potential as Topoisomerase IIa inhibitors. Topo II and Drug Screening kits for the analysis of enzyme reactivity and DNA cleavage were provided by TopoGEN.
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.