L-Serin-diazoacetat

Gefahreninformationscode (GHS)

• Bildanzeige (GHS)

  

• Alarmwort

  Achtung

• Gefahrenhinweise

  H301：Giftig bei Verschlucken.

  H351：Kann vermutlich Krebs verursachen.

• Sicherheit

  P201：Vor Gebrauch besondere Anweisungen einholen.

AZASERINE Chemische Eigenschaften,Einsatz,Produktion Methoden

• R-Sätze Betriebsanweisung:

  R25:Giftig beim Verschlucken.
  R40:Verdacht auf krebserzeugende Wirkung.

• S-Sätze Betriebsanweisung:

  S53:Exposition vermeiden - vor Gebrauch besondere Anweisungen einholen.
  S36/37/39:Bei der Arbeit geeignete Schutzkleidung,Schutzhandschuhe und Schutzbrille/Gesichtsschutz tragen.
  S45:Bei Unfall oder Unwohlsein sofort Arzt zuziehen (wenn möglich, dieses Etikett vorzeigen).

• Chemische Eigenschaften

  Light-yellow needles from EtOH.

• Originator

  Azaserine,TG International Chemical Co.

• Verwenden

  antineoplastic, amino acid antagonist

• Verwenden

  Reagent used to induce pancreatic cancer in experimental animal models.

• Definition

  ChEBI: A carboxylic ester resulting from the formal condensation of the carboxy group of diazoacetic acid with the alcoholic hydroxy group of L-serine. An antibiotic produced by a Streptomyces species.

• Manufacturing Process

  The azaserine is produced by microbiological synthesis using culture of Streptoniyces fragili:
  10 gallons of a nutrient medium having the following composition (%):glucose 1.0, soybean expeller oil meal 1.0, acid hydrolyzed casein 0.5, debittered yeast 0.5, sodium chloride 0.5, water sufficient to make 100.0% is placed in a 30 gallon stainless steel fermenter, the pH adjusted to 7.5 with 6 N sodium hydroxide solution and 0.1% calcium carbonate added. The medium is sterilized by heating at 121°C for 30 min after which the pH of the medium is 6.85. The medium is cooled and inoculated with the spares from two fourteen day old Moyer's sporulation agar slant cultures of Streptoniyces fragilis suspended in 20 ml of sterile 0.01% castile soap solution. The culture mixture is incubated at 27°C for 24 h during which time aeration is supplied through a sparger at the rate of one volume of air per volume of medium per minute.
  The incubated culture thus obtained is used to inoculate the main culture as described below. 150 gallons of a medium having the following composition (%): glucose 1.0, soybean expeller oil meal 1.0, acid hydrolyzed casein 0.5, debittered yeast 0.5, sodium chloride 0.5, ammonium nitrate 0.25, water sufficient to make 100.0 percent. 6 N sodium hydroxide solution-sufficient to bring the pH to 7.5,calcium carbonate - (added after pH adjustment) is placed in a 200-gallon stainless steel fermenter and sterilized by heating at 121°C for 30 min. The medium is cooled, inoculated with the 10-gallon culture of Streptomyces fragilis prepared as described above, and incubated at 26°C for 44 h. During the incubation period air is supplied through a sparger at the rate of 1.5-volumes of air per volume of medium per min and the mixture stirred at the rate of 150 r.p.m. for the first 12 h and at 300 r.p.m. for the final 32 h, 1.5 gallons of a sterilized mixture of crude lard and mineral oils containing mono- and diglycerides being added as needed to control foaming.
  The solid material present in the incubated fermentation mixture is removed by filtration and the filter cake washed with water. The washings are combined with the main filtrate and 110 gallons of this solution stirred with 2079.0 g of activated carbon for about 1 h. The carbon is removed by filtration and the filter cake washed with deionized water. The combined filtrate and washes (136 gallons) are concentrated in vacuum to a volume of about 20 gallons. Three volumes of acetone are added to the concentrate with stirring, and the precipitate which forms removed by filtration and the filter cake washed with 75% aqueous acetone. The combined aqueous acetone filtrate and washings is concentrated in vacuum to a volume of about 19.5 gallons, the concentrate so obtained frozen and dried from the frozen state under high vacuum. 1.0 kg of dry powder is extracted with one 10-liter portion of 90% (by volume) ethanol followed by extraction with one 2-liter portion of the same solvent. The combined extracts (about 12 L) are diluted with sufficient water to reduce the ethanol concentration to 75% by volume, and this alcoholic solution passed through an adsorption column prepared as described below.
  3.0 kg of alumina are stirred with dilute hydrochloric acid so that the pH remains constant at 7.7. The alumina is removed, washed with water and activated by heating at 200°C for 4 h. The alumina is stirred with 75% aqueous ethanol and packed into an adsorption column having a diameter of 4 inches. The total packed volume is approximately 3500 ml.
  The alcoholic solution prepared above is added to the adsorption column at the rate of 6 L/h and the percolate discorded. The column is washed with 35 L of 75% ethanol (by volume), the washing discarded and the column finally washed with 21 L of 50% ethanol. Some O-diazoacetyl-L-serine may be detected in the last wash solution. After the washing has been completed the adsorbed O-diazoacetyl-L-serine is eluted from the

• Therapeutic Function

  Antineoplastic, Antifungal

• Allgemeine Beschreibung

  Pale yellow to green crystals. Used as an antifungal agent.

• Air & Water Reaktionen

  Very soluble in water.

• Reaktivität anzeigen

  AZASERINE is incompatible with acids.

• Hazard

  Toxic; possible carcinogen; neoplastigenic; tumorigenic; poison; teratogen; mutagen.

• Biologische Aktivität

  azaserine, as a naturally occurring serine derivative diazo compound, functions as a purine antagonist and structural analogue of glutamine that inhibits enzymatic activities involving in the pathways of glutamine metabolism. azaserine, an antibiotic and antitumor agent, is used as a potential antineoplastic agent in clinical studies. azaserine dampens the biosynthesis of purine via reacting with cysteine residues in the enzyme active sites. in addition, azaserine triggers dna damage by the formation of carboxymethylated bases and o6-methylguanine.

• Sicherheitsprofil

  Suspected carcinogen with experimental carcinogenic, neoplastigenic, and tumorigenic data. Poison by ingestion, intraperitoneal, and subcutaneous routes. An experimental teratogen. Other experimental reproductive effects. Human mutation data reported. When heated to decomposition it emits toxic fumes of NOx.

• in vitro

  azaserine showed cytotoxicity in raji cells, which was partly due to inhibition of de novo purine biosynthesis, and the expression of o6-methylguanine-dna methyltransferase did not provide protection against cell killing, suggesting that o6-methylguanine was not a major contributor to the cytotoxic dna damage triggered by azaserine. azaserine killed the raji hypoxanthine-guanine phosphoribosyltransferas-deficient(hprt-) mex- cells. in contrast, the raji hprt+ mex- cells were more resistant to azaserine. additionally, azaserine blocked the growth of raji hprt+ mex-cells when treated with 300 μm [1].

• in vivo

  cd-l mice and w/lew rats were injected intraperitoneally with azaserine at a dose of 10 mg/kg body weight once a week for 5 weeks. after 6 months, compared to the control rats and mice, the azaserine-treated animals had a slightly higher incidence of pancreatic atypical acinar cell nodules (aacn) and the average size of aacn of azaserine-treated animals was larger. in addition, the concentration of [14c] azaserine and/or its metabolites was lower in mouse pancreas than in rat pancreas [2].

• IC 50

  7 μm: inhibits parasite growth.

• läuterung methode

  Crystallise azaserine from 90% EtOH. Also dissolve it in H2O, filter it through Supercel and add EtOH to give azaserine as pale yellow crystals. [Greenstein & Winitz The Chemistry of the Amino Acids J. Wiley, Vol 1 pp 75-76 1961, Curphey & David J Org Chem 43 4666 1978, Beilstein 4 IV 3124.]

• Einzelnachweise

  [1]. o'driscoll, m., macpherson, p., xu, y., & karran, p. the cytotoxicity of dna carboxymethylation and methylation by the model carboxymethylating agent azaserine in human cells. carcinogenesis. 1999; 20(9): 1855-1862.
  [2]. b. d. roebuck, herman s. lilja, thomas j. curphey, daniel s. longnecker; pathologic and biochemical effects of azaserine in inbred wistar/lewis rats and noninbred cd-1 mice. j natl cancer inst. 1980; 65 (2): 383-389.

AZASERINE Upstream-Materialien And Downstream Produkte

L-Serin-diazoacetat Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

Global(100)Suppliers

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