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Chemical Compound Review

NSC45383     (4E)-5-amino-6-(7-amino-6- methoxy-5,8...

Synonyms: NCIMech_000191, CCG-35398, CCG-36481, NSC-56748, NSC-83950, ...
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Disease relevance of Nigrin


High impact information on Nigrin

  • Complementation group D A-T fibroblasts were transfected with an episomal vector-based human cDNA library, approximately 610,000 resultant transformants were treated with the radiomimetic drug streptonigrin-resistant, and nine unrelated cDNAs were recovered from 29 surviving streptonigrin-resistant clones [5].
  • Induction of mammalian DNA topoisomerase II dependent DNA cleavage by antitumor antibiotic streptonigrin [6].
  • A linear dose-dependent cell survival was observed for both normal and A-T cells exposed to streptonigrin (up to 1.5 ng/ml) for 3-hr, with the A-T cells being about twice as sensitive as were the normal cells (Do approximately 0.25 ng compared with Do approximately 0.5 ng) [1].
  • ES936 abrogates the toxicity of streptonigrin, with greater effects seen in cell lines expressing higher levels of NQO1 [7].
  • The interaction of volkensin with HeLa cells was compared to that of nigrin b, as an example of a type 2 RIP with low toxicity, and of ricin, as a reference toxin [8].

Chemical compound and disease context of Nigrin


Biological context of Nigrin

  • Finally, chromosomes from both A-T lymphocytes and fibroblasts show about a doubling of breakage rate following exposure to streptonigrin [1].
  • Nigrin b and volkensin bound to cells with comparable affinity (approx. 10(-10) M) and had a similar number of binding sites (2 x 10(5)/cell), two-log lower than that reported for ricin [8].
  • An S. pneumoniae strain containing a defined mutation in pit has impaired growth in medium containing the iron chelator ethylenediamine di-o-hydroxyphenylacetic acid, reduced sensitivity to the iron-dependent antibiotic streptonigrin, and impaired virulence in a mouse model of S. pneumoniae systemic infection [14].
  • We show that both NM3 and UV40 are also hypersensitive to other DNA crosslinking agents (including diepoxybutane and chlorambucil) and to non-crosslinking DNA damaging agents (including bleomycin, streptonigrin and EMS), and that all these sensitivities are all corrected upon transfection of the human FANCG/XRCC9 cDNA [15].
  • Ataxia telangiectasia (A-T) cells are unusually sensitive to streptonigrin, but we show here that they can perform excision repair, as demonstrated by UDS, at the same level as normal cells following exposure to the drug [16].

Anatomical context of Nigrin


Associations of Nigrin with other chemical compounds


Gene context of Nigrin

  • Streptonigrin, a compound known to cause redox cycling in the presence of NQO1, decreased clonogenic survival and decreased anchorage-independent growth in soft agar [13].
  • Cells deleted for Brca2 exon 27 are hypersensitive to gamma-radiation, streptonigrin, mitomycin C and camptothecin and mildly resistant to ICRF-193 which is similar to HR defective cells null for Rad54 [25].
  • Isolation by streptonigrin enrichment and characterization of a transferrin-specific iron uptake mutant of Neisseria meningitidis [26].
  • The feoB mutant was also 2.5 logs more resistant to streptonigrin than wild-type 130b, confirming its decreased ability to acquire iron during extracellular growth [27].
  • Mutation of either sirA or sirB increased the resistance of iron-starved S. aureus to streptonigrin and resulted in compromised growth in iron-restricted, but not iron-rich, media [28].

Analytical, diagnostic and therapeutic context of Nigrin

  • Compounds such as mitomycin C and streptonigrin are efficiently bioactivated by NQO1 and have been used in an enzyme-directed approach to chemotherapy [29].
  • Using absorption, circular dichroism, and fluorescence measurements, we have shown that streptonigrin forms with Au(III) a 1:1 Au(III)-streptonigrin complex [30].
  • Anti-PiaA and anti-PiuA polyclonal rabbit antibodies bound to the surface of live S. pneumoniae when assessed by flow cytometry but did not inhibit growth of S. pneumoniae in cation-depleted medium or bacterial susceptibility to the iron-dependent antibiotic streptonigrin [31].
  • Confocal microscopy showed the rapid localization of volkensin in the Golgi stacks with a perinuclear localization similar to that of ricin, while nigrin b was distributed between cytoplasmic dots and the Golgi compartment [8].
  • To investigate the chemosensitivity of A-T heterozygote cell lines, we used TUNEL to analyse the level of apoptosis after drug treatment with etoposide and streptonigrin [32].


  1. Effects of the DNA strand-cleaving antitumor agent, streptonigrin, on ataxia telangiectasia cells. Taylor, A.M., Flude, E., Garner, C.M., Campbell, J.B., Edwards, M.J. Cancer Res. (1983) [Pubmed]
  2. Metabolism of bioreductive antitumor compounds by purified rat and human DT-diaphorases. Beall, H.D., Mulcahy, R.T., Siegel, D., Traver, R.D., Gibson, N.W., Ross, D. Cancer Res. (1994) [Pubmed]
  3. Induction of glucocorticoid-resistant variants in a murine thymoma line by antitumor drugs. Huet-Minkowski, M., Gasson, J.C., Bourgeois, S. Cancer Res. (1981) [Pubmed]
  4. Bacteria form intracellular free radicals in response to paraquat and streptonigrin. Demonstration of the potency of hydroxyl radical. Hassett, D.J., Britigan, B.E., Svendsen, T., Rosen, G.M., Cohen, M.S. J. Biol. Chem. (1987) [Pubmed]
  5. Expression cloning of multiple human cDNAs that complement the phenotypic defects of ataxia-telangiectasia group D fibroblasts. Meyn, M.S., Lu-Kuo, J.M., Herzing, L.B. Am. J. Hum. Genet. (1993) [Pubmed]
  6. Induction of mammalian DNA topoisomerase II dependent DNA cleavage by antitumor antibiotic streptonigrin. Yamashita, Y., Kawada, S., Fujii, N., Nakano, H. Cancer Res. (1990) [Pubmed]
  7. Biochemical, cytotoxic, and genotoxic effects of ES936, a mechanism-based inhibitor of NAD(P)H:quinone oxidoreductase 1, in cellular systems. Dehn, D.L., Siegel, D., Swann, E., Moody, C.J., Ross, D. Mol. Pharmacol. (2003) [Pubmed]
  8. Interaction of volkensin with HeLa cells: binding, uptake, intracellular localization, degradation and exocytosis. Battelli, M.G., Musiani, S., Buonamici, L., Santi, S., Riccio, M., Maraldi, N.M., Girbés, T., Stirpe, F. Cell. Mol. Life Sci. (2004) [Pubmed]
  9. A tryptophan C-methyltransferase involved in streptonigrin biosynthesis in Streptomyces flocculus. Hartley, D.L., Speedie, M.K. Biochem. J. (1984) [Pubmed]
  10. Role of extracellular iron in the action of the quinone antibiotic streptonigrin: mechanisms of killing and resistance of Neisseria gonorrhoeae. Cohen, M.S., Chai, Y., Britigan, B.E., McKenna, W., Adams, J., Svendsen, T., Bean, K., Hassett, D.J., Sparling, P.F. Antimicrob. Agents Chemother. (1987) [Pubmed]
  11. Response of Pseudomonas aeruginosa to pyocyanin: mechanisms of resistance, antioxidant defenses, and demonstration of a manganese-cofactored superoxide dismutase. Hassett, D.J., Charniga, L., Bean, K., Ohman, D.E., Cohen, M.S. Infect. Immun. (1992) [Pubmed]
  12. Purification and characterization of S-adenosylhomocysteine deaminase from streptonigrin-producing Streptomyces flocculus. Zulty, J.J., Speedie, M.K. J. Bacteriol. (1989) [Pubmed]
  13. Targeting NAD(P)H:quinone oxidoreductase (NQO1) in pancreatic cancer. Lewis, A.M., Ough, M., Hinkhouse, M.M., Tsao, M.S., Oberley, L.W., Cullen, J.J. Mol. Carcinog. (2005) [Pubmed]
  14. Characterization of pit, a Streptococcus pneumoniae iron uptake ABC transporter. Brown, J.S., Gilliland, S.M., Ruiz-Albert, J., Holden, D.W. Infect. Immun. (2002) [Pubmed]
  15. The Chinese hamster FANCG/XRCC9 mutant NM3 fails to express the monoubiquitinated form of the FANCD2 protein, is hypersensitive to a range of DNA damaging agents and exhibits a normal level of spontaneous sister chromatid exchange. Wilson, J.B., Johnson, M.A., Stuckert, A.P., Trueman, K.L., May, S., Bryant, P.E., Meyn, R.E., D'Andrea, A.D., Jones, N.J. Carcinogenesis (2001) [Pubmed]
  16. Unscheduled DNA synthesis induced by streptonigrin in ataxia telangiectasia fibroblasts. Taylor, A.M., Laher, H.B., Morgan, G.R. Carcinogenesis (1985) [Pubmed]
  17. Isolation and partial characterization of nigrin b, a non-toxic novel type 2 ribosome-inactivating protein from the bark of Sambucus nigra L. Girbés, T., Citores, L., Ferreras, J.M., Rojo, M.A., Iglesias, R., Muñoz, R., Arias, F.J., Calonge, M., García, J.R., Méndez, E. Plant Mol. Biol. (1993) [Pubmed]
  18. The effect of washing lymphocytes after in vivo treatment with streptonigrin on the yield of chromosome and chromatid aberrations in blood cultures. Dufrain, R.J., Littlefield, L.G., Wilmer, J.L. Mutat. Res. (1980) [Pubmed]
  19. The kinetics of chromosome and DNA damage by streptonigrin in CHO cells. Testoni, M.I., Bianchi, N.O., Bianchi, M.S. Mutat. Res. (1995) [Pubmed]
  20. Evaluation of chemically induced cytogenetic lesions in rabbit oocytes. III. A postimplantation analysis of streptonigrin effects. DuFrain, R.J., Littlefield, L.G., Morrison, W.D., Huff, V.D., Hutton, D. Mutat. Res. (1984) [Pubmed]
  21. Iron requirement in the bactericidal mechanism of streptonigrin. Yeowell, H.N., White, J.R. Antimicrob. Agents Chemother. (1982) [Pubmed]
  22. Enhancement of chromosome aberrations by the combination of DNA substitution with halogenated deoxyuridine and streptonigrin treatments. Testoni, M.I., López-Camelo, J.S., Bianchi, M.S., Bianchi, N.O. Mutat. Res. (1996) [Pubmed]
  23. Photogeneration of superoxide and decarboxylated peptide radicals by carboquone, mitomycin C and streptonigrin. An electron spin resonance and spin trapping study. Carmichael, A.J., Samuni, A., Riesz, P. Photochem. Photobiol. (1985) [Pubmed]
  24. Application of chromosome painting to clastogenicity testing in vitro. Marshall, R., Obe, G. Environ. Mol. Mutagen. (1998) [Pubmed]
  25. Embryonic stem cells deficient for Brca2 or Blm exhibit divergent genotoxic profiles that support opposing activities during homologous recombination. Marple, T., Kim, T.M., Hasty, P. Mutat. Res. (2006) [Pubmed]
  26. Isolation by streptonigrin enrichment and characterization of a transferrin-specific iron uptake mutant of Neisseria meningitidis. Dyer, D.W., McKenna, W., Woods, J.P., Sparling, P.F. Microb. Pathog. (1987) [Pubmed]
  27. Legionella pneumophila feoAB promotes ferrous iron uptake and intracellular infection. Robey, M., Cianciotto, N.P. Infect. Immun. (2002) [Pubmed]
  28. Involvement of SirABC in iron-siderophore import in Staphylococcus aureus. Dale, S.E., Sebulsky, M.T., Heinrichs, D.E. J. Bacteriol. (2004) [Pubmed]
  29. A new screening system for NAD(P)H:quinone oxidoreductase (NQO1)-directed antitumor quinones: identification of a new aziridinylbenzoquinone, RH1, as a NQO1-directed antitumor agent. Winski, S.L., Hargreaves, R.H., Butler, J., Ross, D. Clin. Cancer Res. (1998) [Pubmed]
  30. Bifunctional antitumor compounds: synthesis and characterization of a Au(III)-streptonigrin complex with thiol-modulating properties. Moustatih, A., Garnier-Suillerot, A. J. Med. Chem. (1989) [Pubmed]
  31. Antibodies to the iron uptake ABC transporter lipoproteins PiaA and PiuA promote opsonophagocytosis of Streptococcus pneumoniae. Jomaa, M., Yuste, J., Paton, J.C., Jones, C., Dougan, G., Brown, J.S. Infect. Immun. (2005) [Pubmed]
  32. ATM heterozygote cells exhibit intermediate levels of apoptosis in response to streptonigrin and etoposide. Pernin, D., Bay, J.O., Uhrhammer, N., Bignon, Y.J. Eur. J. Cancer (1999) [Pubmed]
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