Article: Inhibition of DNA synthesis by nitroheterocycles. I. Correlation with half-wave reduction potential

Twenty-one nitroheterocycles, including metronidazole, misonidazole and AF-2, were tested for their ability to inhibit DNA synthesis in mouse L-929 cells growing in culture. All those tested inhibited the rate of incorporation of 3H-thymidine into L cells following drug treatment for 4 h under aerobic conditions. Only 4 drugs reached their limits of solubility before the uptake of 3H-thymidine was inhibited by 50% or more. For the remaining 17, the log of the concentration producing 50% inhibition of incorporation was directly correlated with the half-wave reduction potential of the compound.

Citing Articles

Metronidazole decreases viability of DLD-1 colorectal cancer cell line.

Sadowska A, Kretowski R, Szynaka B, Cechowska-Pasko M, Car H Cancer Biother Radiopharm. 2013; 28(8):615-22.

PMID: 23777253 PMC: 3777553. DOI: 10.1089/cbr.2013.1485.

Isobutyl 3,5-dinitro-benzoate.

Zou P, Xie M, Luo S, Liu Y, He Y Acta Crystallogr Sect E Struct Rep Online. 2011; 65(Pt 4):o878.

PMID: 21582589 PMC: 2968849. DOI: 10.1107/S1600536809010381.

Interaction of nitroimidazole drugs with DNA in vitro: structure-activity relationships.

Knox R, Knight R, Edwards D Br J Cancer. 1981; 44(5):741-5.

PMID: 7032569 PMC: 2010832. DOI: 10.1038/bjc.1981.261.

Structure-activity relationships in the free-radical metabolism of xenobiotics.

Chignell C Environ Health Perspect. 1985; 61:133-7.

PMID: 2998746 PMC: 1568756. DOI: 10.1289/ehp.8561133.

Inhibition of DNA synthesis by nitroheterocycles. II. Mechanisms of cytotoxicity.

Olive P Br J Cancer. 1979; 40(1):94-104.

PMID: 475964 PMC: 2009955. DOI: 10.1038/bjc.1979.145.

References

1.

Wardman P, Clarke E . Oxygen inhibition of nitroreductase: electron transfer from nitro radical-anions to oxygen. Biochem Biophys Res Commun. 1976; 69(4):942-9. DOI: 10.1016/0006-291x(76)90464-2. View

2.

Mason R, Holtzman J . The mechanism of microsomal and mitochondrial nitroreductase. Electron spin resonance evidence for nitroaromatic free radical intermediates. Biochemistry. 1975; 14(8):1626-32. DOI: 10.1021/bi00679a013. View

3.

Sealy R, Swartz H, Olive P . Electron spin resonance-spin trapping. Detection of superoxide formation during aerobic microsomal reduction of nitro-compounds. Biochem Biophys Res Commun. 1978; 82(2):680-4. DOI: 10.1016/0006-291x(78)90928-2. View

4.

Lu C, McCalla D . Action of some nitrofuran derivatives on glucose metabolism, ATP levels, and macromolecule synthesis in Escherichia coli. Can J Microbiol. 1978; 24(6):650-7. DOI: 10.1139/m78-109. View

5.

Olive P, Durand R . Activation of radiosensitizers by hypoxic cells. Br J Cancer Suppl. 1978; 3:124-8. PMC: 2149417. View

Inhibition of DNA Synthesis by Nitroheterocycles. I. Correlation with Half-wave Reduction Potential