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The clinical anticancer agent mitoxantrone is subject to irreversible oxidation by hydrogen peroxide catalyzed by horseradish peroxidase (HRP). The characteristic absorption changes that result provide evidence for an initial metabolite which is further oxidized enzymatically. The formation of the metabolite is accompanied by the concomitant generation of a… (More)
Ambient temperature incubation of the anticancer agent mitoxantrone with horseradish peroxidase and hydrogen peroxide converts it into a hexahydronaphtho[2,3-f]quinoxaline-7,12-dione in which one side chain has cyclized to the chromophore. The structure of this cyclic metabolite was secured by independent synthesis. This peroxidative conversion of… (More)
The antitumor agent mitoxantrone undergoes horseradish peroxidase-catalyzed oxidation by hydrogen peroxide to an identifiable cyclic metabolite which is a substituted hexahydronaphtho[2,3-f]-quinoxaline-7,12-dione. Binding of mitoxantrone to DNA inhibited enzymatic oxidation of the drug. The metabolite of mitoxantrone, derived from the action of the… (More)
A cell line of Catharanthus roseus (L.) G. Don coded PRL # 200, was characterized with respect to its biosynthetic capabilities for indolealkaloids, in particular catharanthine, in suspension cultures. Other alkaloids isolated are vallesiachotamine isomers, ajmalicine, hörhammericine, hörhammerinine, vindolinine, 19-epivindolinine and strictosidine lactam.
Daunorubicin can bind Cu (II) in Tris-HCl buffer (pH 7.4) and in the presence of NADH (100 microM). The complex is very stable. Cu (II) is not removed from the complex by cytochrome c reductase. The complexation of Cu (II) to daunorubicin gives rise to a modification of its redox properties. The complex, unlike the free drug, does not stimulate oxygen… (More)
EPR and spin-trapping techniques were employed to study the oxidation of the dihydronicotinamide adenine dinucleotide (NADH) photosensitized by an anthrapyrazole-antitumor agent. The superoxide radical was detected as a DMPO adduct upon illumination of the system with visible light. Photoinduced generation of hydroxyl radicals is demonstrated by detection… (More)
A novel anthrapyrazole anticancer agent has been examined for photosensitizing properties. Illumination of the anthrapyrazole and ascorbic acid with blue light in aerated aqueous solutions causes SOD and catalase-sensitive oxygen consumption, indicating involvement of both superoxide radical and hydrogen peroxide in this process. Electron paramagnetic… (More)