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Reductive activation of potential antitumor bis(aziridinyl)benzoquinones by xanthine oxidase: competition between oxygen reduction and quinone reduction. 1990

K J Lusthof, and W Richter, and N J de Mol, and L H Janssen, and W Verboom, and D N Reinhoudt
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Utrecht, The Netherlands.

The reduction of a series of 2,5-bis(1-aziridinyl)-1,4-benzoquinone (BABQ) derivatives with various 3,6 substituents by the enzyme xanthine oxidase has been studied. The reduction rate has been assayed by measuring the rate of reduction of cytochrome c, which is very efficiently reduced by reduced BABQ species. Under nitrogen, the reduction rate correlated with the quinone reduction potential and steric parameters. Comparing reduction rates under nitrogen and air demonstrates that at BABQ concentrations greater than 25 microM the competition for electrons from xanthine oxidase between oxygen and the BABQ derivative is dominated by the latter. This is also confirmed by the effect of superoxide dismutase (SOD): in the presence of a BABQ derivative, cytochrome c reduction can be totally inhibited by SOD, although the required amount of SOD depends on the redox potential of the quinones. This indicates that SOD causes the equilibrium between semiquinone and superoxide to shift, resulting in a decrease of the semiquinone concentration. It is concluded that reduction by xanthine oxidase is a simple and effective method for reducing aziridinylbenzoquinones.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D010084 Oxidation-Reduction A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). Redox,Oxidation Reduction
D002374 Catalase An oxidoreductase that catalyzes the conversion of HYDROGEN PEROXIDE to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in ACATALASIA. Catalase A,Catalase T,Manganese Catalase,Mn Catalase
D003574 Cytochrome c Group A group of cytochromes with covalent thioether linkages between either or both of the vinyl side chains of protoheme and the protein. (Enzyme Nomenclature, 1992, p539) Cytochromes Type c,Group, Cytochrome c,Type c, Cytochromes
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D001388 Aziridines Saturated azacyclopropane compounds. They include compounds with substitutions on CARBON or NITROGEN atoms. Ethyleneimines,Azacyclopropanes, Saturated,Dimethyleneimines,Saturated Azacyclopropanes
D001711 Biotransformation The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D013482 Superoxide Dismutase An oxidoreductase that catalyzes the reaction between SUPEROXIDES and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. Hemocuprein,Ag-Zn Superoxide Dismutase,Cobalt Superoxide Dismutase,Cu-Superoxide Dismutase,Erythrocuprein,Fe-Superoxide Dismutase,Fe-Zn Superoxide Dismutase,Iron Superoxide Dismutase,Manganese Superoxide Dismutase,Mn-SOD,Mn-Superoxide Dismutase,Ag Zn Superoxide Dismutase,Cu Superoxide Dismutase,Dismutase, Ag-Zn Superoxide,Dismutase, Cobalt Superoxide,Dismutase, Cu-Superoxide,Dismutase, Fe-Superoxide,Dismutase, Fe-Zn Superoxide,Dismutase, Iron Superoxide,Dismutase, Manganese Superoxide,Dismutase, Mn-Superoxide,Dismutase, Superoxide,Fe Superoxide Dismutase,Fe Zn Superoxide Dismutase,Mn SOD,Mn Superoxide Dismutase,Superoxide Dismutase, Ag-Zn,Superoxide Dismutase, Cobalt,Superoxide Dismutase, Fe-Zn,Superoxide Dismutase, Iron,Superoxide Dismutase, Manganese
D014969 Xanthine Oxidase An iron-molybdenum flavoprotein containing FLAVIN-ADENINE DINUCLEOTIDE that oxidizes hypoxanthine, some other purines and pterins, and aldehydes. Deficiency of the enzyme, an autosomal recessive trait, causes xanthinuria. Hypoxanthine Oxidase,Hypoxanthine Dehydrogenase,Hypoxanthine-Xanthine Oxidase,Purine-Xanthine Oxidase,Dehydrogenase, Hypoxanthine,Hypoxanthine Xanthine Oxidase,Oxidase, Hypoxanthine,Oxidase, Hypoxanthine-Xanthine,Oxidase, Purine-Xanthine,Oxidase, Xanthine,Purine Xanthine Oxidase

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