Structure-activity Relationships in the Free-radical Metabolism of Xenobiotics

Overview

Journal Environ Health Perspect

Date 1985 Sep 1

PMID 2998746

Citations 2

Authors

C F Chignell

Affiliations

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Abstract

Many xenobiotics, including naturally occurring compounds, drugs, and environmental agents, are metabolized both in vivo and in vitro to free-radical intermediates. The one-electron reduction of nitroaromatic compounds, quinones, and a wide variety of other chemicals is catalyzed enzymatically by a number of reductases and dehydrogenases. Structure-activity studies have shown that the cytotoxicities of nitroaromatic compounds and quinones are related to their one-electron reduction potentials (E1(7)). Other factors such as oil:water partition coefficients may also be important. Xenobiotics may also be oxidized to free radicals by peroxidases. Hammett's rules apply to the one-electron oxidation of simple meta- or para-substituted phenols and amines by horseradish peroxidase, compound I.

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References

Asquith J, Watts M, Patel K, Smithen C, Adams G . Electron affinic sensitization. V. Radiosensitization of hypoxic bacteria and mammalian cells in vitro by some nitroimidazoles and nitropyrazoles. Radiat Res. 1974; 60(1):108-18. View

Docampo R, Moreno S, Mason R . Generation of free radical metabolites and superoxide anion by the calcium indicators arsenazo III, antipyrylazo III, and murexide in rat liver microsomes. J Biol Chem. 1983; 258(24):14920-5. View

GRUNBERG E, TITSWORTH E . Chemotherapeutic properties of heterocyclic compounds: monocyclic compounds with five-membered rings. Annu Rev Microbiol. 1973; 27:317-46. DOI: 10.1146/annurev.mi.27.100173.001533. View

Bus J, Aust S, Gibson J . Superoxide- and singlet oxygen-catalyzed lipid peroxidation as a possible mechanism for paraquat (methyl viologen) toxicity. Biochem Biophys Res Commun. 1974; 58(3):749-55. DOI: 10.1016/s0006-291x(74)80481-x. View

Handa K, Sato S . Generation of free radicals of quinone group-containing anti-cancer chemicals in NADPH-microsome system as evidenced by initiation of sulfite oxidation. Gan. 1975; 66(1):43-7. View

Mason R, Holtzman J . The role of catalytic superoxide formation in the O2 inhibition of nitroreductase. Biochem Biophys Res Commun. 1975; 67(4):1267-74. DOI: 10.1016/0006-291x(75)90163-1. View

Job D, Dunford H . Substituent effect on the oxidation of phenols and aromatic amines by horseradish peroxidase compound I. Eur J Biochem. 1976; 66(3):607-14. DOI: 10.1111/j.1432-1033.1976.tb10588.x. View

Adams G, Clarke E, Jacobs R, Stratford I, Wallace R, Wardman P . Mammalian cell toxicity of nitro compounds : dependence upon reduction potential. Biochem Biophys Res Commun. 1976; 72(3):824-9. DOI: 10.1016/s0006-291x(76)80207-0. View

Myers C, McGuire W, Young R . Adriamycin: amelioration of toxicity by alpha-tocopherol. Cancer Treat Rep. 1976; 60(7):961-2. View

10.

Handa K, Sato S . Stimulation of microsomal NADPH oxidation by quinone group-containing anticancer chemicals. Gan. 1976; 67(4):523-8. View

11.

Goldstein B, CAVALLERI B, Zerilli L, Carniti G, Silvestri L . The mechanism of action of nitro-heterocyclic antimicrobial drugs. Metabolic activation by micro-organisms. J Gen Microbiol. 1977; 100(2):283-98. DOI: 10.1099/00221287-100-2-283. View

12.

Bachur N, Gordon S, Gee M . Anthracycline antibiotic augmentation of microsomal electron transport and free radical formation. Mol Pharmacol. 1977; 13(5):901-10. View

13.

Lai C, Piette L . Hydroxyl radical production involved in lipid peroxidation of rat liver microsomes. Biochem Biophys Res Commun. 1977; 78(1):51-9. DOI: 10.1016/0006-291x(77)91220-7. View

14.

Sato S, Iwaizumi M, Handa K, Tamura Y . Electron spin resonance study on the mode of generation of free radicals of daunomycin, adriamycin, and carboquone in NAD(P)H-microsome system. Gan. 1977; 68(5):603-8. View

15.

Bachur N, Gordon S, Gee M . A general mechanism for microsomal activation of quinone anticancer agents to free radicals. Cancer Res. 1978; 38(6):1745-50. View

16.

Chin J, Sheinin D, Rauth A . Screening for the mutagenicity of nitro-group containing hypoxic cell radiosensitizers using Salmonella typhimurium strains TA 100 and TA98. Mutat Res. 1978; 58(1):1-10. View

17.

Chessin H, McLaughlin T, Mroczkowski Z, RUPP W, Low K . Radiosensitization, mutagenicity, and toxicity of Escherichia coli by several nitrofurans and nitroimidazoles. Radiat Res. 1978; 75(2):424-31. View

18.

Olive P . Inhibition of DNA synthesis by nitroheterocycles. I. Correlation with half-wave reduction potential. Br J Cancer. 1979; 40(1):89-93. PMC: 2009968. DOI: 10.1038/bjc.1979.144. View

19.

Hassan H, Fridovich I . Intracellular production of superoxide radical and of hydrogen peroxide by redox active compounds. Arch Biochem Biophys. 1979; 196(2):385-95. DOI: 10.1016/0003-9861(79)90289-3. View

20.

Adams G, Stratford I, Wallace R, Wardman P, Watts M . Toxicity of nitro compounds toward hypoxic mammalian cells in vitro: dependence on reduction potential. J Natl Cancer Inst. 1980; 64(3):555-60. View