Streptonigrin

Streptonigrin is a phenylpyridylquinoline originally isolated from S. flocculus with diverse biological activities. Streptonigrin (2.5-12.5 μM) induces DNA cleavage by calf thymus topoisomerase II in a concentration-dependent manner. It induces phage production in S. typhimurium when used at concentrations ranging from 1 to 10 μg/ml. 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. 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. Streptonigrin (0.001-0.1 μg/ml) inhibits mitosis and induces chromatin breaks in human leukocytes in a concentration-dependent manner. In vivo, streptonigrin (0.05 mg/kg, i.p.) increases the mean survival time in rats infected with Rauscher virus.

Brown to red solid. Soluble in polar solvents and alkaline solutions; insoluble in most nonpolar solvents and acid solutions.

Streptonigrin is an aminoquinone antitumour antibiotic. Its antineoplastic activity requires reductive activation by Xanthine-converting enzymes. It induces apoptosis by a mechanism involving NF-κB. DNA cleavage reaction and chromosome damage by Streptonigrin are influenced by the nature of the metal ion present and dependent on the production of free radicals. Its antibiotic activity is iron-activated. Streptonigrin from Streptomyces flocculus

Streptonigrin is an unusual aminoquinone with broad biological activity against bacteria, fungi, nematodes, viruses and tumour cells. Streptonigrin acts as a bioreductive agent, highly dependent on interactions with metal ions, notably iron, and plays an important role in free radical production through redox cycling of NAD(P)H:quinone oxidoreductase (NQO1).

ChEBI: Complex cytotoxic antibiotic obtained from Streptomyces flocculus or S. rufochronmogenus. It is used in advanced carcinoma and causes leukopenia.

Nigrin (Pfizer).

Streptonigrin (SN) is an aminoquinone antitumour antibiotic. Its antineoplastic activity requires reductive activation by Xanthine-converting enzymes. It induces apoptosis by a mechanism involving NF-κB. DNA cleavage reaction and chromosome damage by SN are influenced by the nature of the metal ion present and dependent on the production of free radicals. Its antibiotic activity is iron-activated.

Streptonigrin is purified by TLC on pH 7-buffered silica gel plates (made from a slurry of Silica Gel 60 and 400mL of 0.05M phosphate buffer pH 7.0) and eluted with 5% MeOH/CHCl3. Material from the extracted band recrystallises from Me2CO or dioxane as almost black plates or needles. It is soluble in pyridine, Me2NCHO, aqueous NaHCO3 (some dec), and slightly soluble in MeOH, EtOH, EtOAc and H2O. It has UV max 248, 375-380nm ( 38,400 and 17,400). [Weinreb et al. J Am Chem Soc 104 536 1982, Rao et al. J Am Chem Soc 85 2532 1963.] Itis antineoplastic and causes severe bone marrow depression [Wilson et al. Antibiot Chemother 11 147 1961].

[1] Y YAMASHITA. Induction of mammalian DNA topoisomerase II dependent DNA cleavage by antitumor antibiotic streptonigrin.[J]. Cancer research, 1990, 50 18: 5841-5844.
[2] MYRON LEVINE  Marcene B. The action of streptonigrin on bacterial DNA metabolism and on induction of phage production in lysogenic bacteria[J]. Virology, 1963, 21 4: Pages 568-574. DOI: 10.1016/0042-6822(63)90228-9
[3] HEATHER Y. YEOWELL J R W. Iron Requirement in the Bactericidal Mechanism of Streptonigrin[J]. Antimicrobial Agents and Chemotherapy, 1983, 23 1: 512-512. DOI: 10.1128/aac.23.3.512
[4] HOWARD D. BEALL . Role of NAD(P)H:Quinone oxidoreductase (DT-diaphorase) in cytotoxicity and induction of DNA damage by streptonigrin[J]. Biochemical pharmacology, 1996, 51 5: Pages 645-652. DOI: 10.1016/s0006-2952(95)00223-5
[5] M M COHEN  A P C  M W SHAW. The effects of streptonigrin on cultured human leukocytes.[J]. Proceedings of the National Academy of Sciences of the United States of America, 1963, 50: 16-24. DOI: 10.1073/pnas.50.1.16
[6] T J MCBRIDE  D W  J J Oleson. The activity of streptonigrin against the Rauscher murine leukemia virus in vivo.[J]. Cancer research, 1966, 26 4: 727-732.