Streptonigrin (Bruneomycin)

Streptonigrin is a phenylpyridylquinoline originally isolated from S. flocculus with diverse biological activities.^1,2,3,4,5,6 Streptonigrin (2.5-12.5 μM) induces DNA cleavage by calf thymus topoisomerase II in a concentration-dependent manner.¹ It induces phage production in S. typhimurium when used at concentrations ranging from 1 to 10 μg/ml.² Streptonigrin (10 μg/ml) inhibits DNA synthesis in and reduces survival of S. typhimurium bacteria. Streptonigrin is bactericidal against E. coli in an iron-dependent manner, an effect that is blocked by the iron chelators deferoxamine and orthophenanthroline.³ Streptonigrin (40 nM) is cytotoxic to human HT-29 colon carcinoma cells but not to BE colon carcinoma cells in which NAD(P)H:quinone oxidoreductase is not expressed.⁴ Streptonigrin (0.001-0.1 μg/ml) inhibits mitosis and induces chromatin breaks in human leukocytes in a concentration-dependent manner.⁵ In vivo, streptonigrin (0.05 mg/kg, i.p.) increases the mean survival time in rats infected with Rauscher virus.⁶

1.Yamashita, Y., Kawada, S., Fujii, N., et al.Induction of mammalian DNA topoisomerase II dependent DNA cleavage by antitumor antibiotic streptonigrinCancer Res.50(18)5841-5844(1990) 2.Levine, M., and Borthwick, M.The action of streptonigrin on bacterial DNA metabolism and on induction of phage production in lysogenic bacteriaVirology21(4)568-574(1963) 3.Yeowell, H.N., and White, J.R.Iron requirement in the bactericidal mechanism of streptonigrinAntimicrob. Agents Chemother.22(6)961-968(1982) 4.Beall, H.D., Liu, Y., Siegel, D., et al.Role of NAD(P)H:quinone oxidoreductase (DT-diaphorase) in cytotoxicity and induction of DNA damage by streptonigrinBiochem. Pharmacol.51(5)645-652(1996) 5.Cohen, M.M., Shaw, M.W., and Craig, A.P.The effects of streptonigrin on cultured human leukocytesProc. Natl. Acad. Sci. USA50(1)16-24(1963) 6.McBride, T.J., Oleson, J.J., and Woolf, D.The activity of streptonigrin against the Rauscher murine leukemia virus in vivoCancer Res.26(4)727-732(1966)