Actinomycin D Chemical Properties
- Melting point:
- 251-253 °C
- Boiling point:
- 848°C (rough estimate)
- 1.0757 (rough estimate)
- refractive index
- 1.5700 (estimate)
- Flash point:
- storage temp.
- ethanol, DMSO: Stable in aqueous solutions at 2-8 °C.soluble
- red, powder
- optical activity
- [α]/D alpha: 28/D (Rotation: -315 degrees (c=0.25% in methanol))
- Water Solubility
- Stable, but light sensitive, especially in dilute solution. Incompatible with strong acids, strong bases, strong oxidizing agents. Combustible.
- CAS DataBase Reference
- 50-76-0(CAS DataBase Reference)
- 3 (Vol. 10, Sup 7) 1987
- EPA Substance Registry System
- Actinomycin D (50-76-0)
- Hazard Codes
- Risk Statements
- Safety Statements
- UN 3462 6.1/PG 2
- WGK Germany
- HS Code
- Hazardous Substances Data
- 50-76-0(Hazardous Substances Data)
- LD50 oral in rat: 7200ug/kg
Actinomycin D Usage And Synthesis
red crystalline powder
Actinomycin D is a combustible, bright red crystalline solid.
Cosmegen,Merck Sharp and Dohme,US,1965
Antibiotic substance belonging to the actinomycin complex, produced by several Streptomyces spp. Antineoplastic
An antineoplastic antibiotic that inhibits cell proliferation by forming a stable complex with DNA and blocking the movement of RNA polymerase which interferes with DNA-dependent RNA synthesis. Induces apoptosis. Potent antitumor agent.
antineoplastic, intercalating agent
Actinomycin D is the most studied member of a family of unique bicyclic depsipeptides produced by several Streptomyces species. The depsipeptides are linked by a heterocyclic benzoxazone "anchor" that gives the metabolites a highly distinctive red/orange colour. Actinomycin D exhibits potent antibiotic and antitumour activity via DNA intercalation leading to the inhibition of nucleic acid synthesis. Tumour cell death has been demonstrated to occur by apoptosis.
Dactinomycin (actinomycin D, Cosmegen) is one of a family of chromopeptides produced by Streptomyces. It is known to bind noncovalently to double-strand DNA by partial intercalation, inhibiting DNA-directed RNA synthesis. The drug is most toxic to proliferating cells, but it is not specific for any one phase of the cell cycle. Resistance to dactinomycin is caused by decreased ability of tumor cells to take up and retain the drug, and it is associated with cross-resistance to vinca alkaloids, the anthracyclines, and certain other agents (multidrug resistance).
An incubated culture of Actinomyces antibioticus was prepared using a
medium consisting of 1% tryptone-peptone, 0.5% starch, 0.2% K2HPO4, 0.2%
NaCl and 0.25% agar in distilled water, grown at a temperature of
approximately 25° to 35°C, the incubation being complete after 6 to 10 days.
50 liters of this incubated culture are extracted approximately six times with
ether, using 20 liters of ether for each extraction.
The final extract is faintly pale yellow in color, whereas the previous extracts are orange. The combined ether extracts are concentrated to dryness and about 3 grams of a reddish-brown residue is obtained. The residue is stirred with approximately 400 cc of petroleum ether for two to three hours, the solvent decanted and the residue treated again with approximately 400 cc of petroleum ether. A pale yellow oil constituting crude actinomycin B is recovered by evaporation from the petroleum ether.
The dark petroleum ether insoluble residue is dissolved in 1 liter of benzene with gentle heating. Usually a small amount of black amorphous material remains undissolved and is filtered off. The benzene solution is permitted to drop through a chromatographic tower (60 x 5 cm) packed with aluminum oxide (according to Brockman). The pigment is readily adsorbed. The column is washed with about 1 liter of benzene during which operation very little migration of the color bands occurs.
The column is then washed with benzene-acetone solution (15:85) whereby a chromatogram develops. By continued washing, light yellow colored pigments pass out of the column. When the main band (orange-red) reaches the lower end of the column, a solution of 30:70 acetone-benzene is passed through the column. The latter solvent elutes the pigment and when the eluate is very pale in color, washing is discontinued.
The eluate is concentrated to dryness under reduced pressure, taken up in 25 cc of hot acetone, filtered, and diluted with ether. The pigment which crystallizes as red-brick colored platelets is essentially pure but may be recrystallized if desired from hot ethyl acetate. An analysis of the product showed C = 59.01; H = 6.81; N = 13.38.
Dactinomycin is available in vials containing 0.5 mg of drugfor reconstitution in sterile water for IV administration Thisantibiotic is most effective in the treatment of rhabdomyosarcomaand Wilms tumor in children as well as in the treatmentof choriocarcinoma, Ewing sarcoma, Kaposi sarcoma, andtesticular carcinoma. The pharmacokinetics of dactinomycinhas not been well characterized, but it appears to concentratein nucleated blood cells. The agent is 5% to 15% plasmaprotein bound and is excreted mostly unchanged in urineand bile. Other metabolites have not been characterized.The terminal elimination half-life is 30 to 40 hours.Myelosuppression is dose limiting with both leucopenia andthrombocytopenia being the most likely presentation. Nauseaand vomiting occur shortly (2 hours) after treatment and maybe severe. Mucositis and diarrhea also result from irritation ofthe GI tract. Hair loss is commonly associated with the agentas is hyperpigmentation of the skin and erythema.
Bright red rhomboid prisms or red powder.
Air & Water Reactions
Actinomycin D can react with strong oxidizing agents, strong acids and strong bases.
Flash point data for Actinomycin D are not available. Actinomycin D is probably combustible.
Anti-neoplastic antibiotic. Inhibits RNA polymerase and is a potent inducer of apoptosis.
Mechanism of action
Dactinomycin is cleared rapidly from plasma, does not enter the brain, is not appreciably metabolized or protein bound, and is gradually excreted in both bile and urine.Virtually no drug is detected in CSF.
Dactinomycin is used in curative combined treatment of Wilms’ tumor, Ewing’s sarcoma, rhabdomyosarcoma, and gestational choriocarcinoma. It is active in testicular tumors, lymphomas, melanomas, and sarcomas, although its use in most of these malignancies has been supplanted by other agents.
The major side effects of dactinomycin are severe nausea, vomiting, and myelosuppression. Mucositis, diarrhea, alopecia, and radiation recall reactions may occur. The drug is immunosuppressive and carcinogenic.
An antibiotic product from streptomyces, used as anticancer and veterinary drug
Veterinary Drugs and Treatments
Dactinomycin has been used as adjunctive treatment of lymphoreticular neoplasms, bone and soft tissue sarcomas, and carcinomas in small animals. It appears to have low efficacy against most carcinomas and sarcomas. It is being investigated as a part of protocols for rescue therapy for canine lymphomas.
UN2811 Toxic solids, organic, n.o.s., Hazard Class: 6.1; Labels: 6.1-Poisonous materials, Technical Name Required.
It crystallises as bright red rhombic crystals from absolute EtOH or from MeOH/EtOH (1:3). It will also crystallise from EtOAc/cyclohexane (m 246-247o dec), CHCl3/pet ether ( m 245-246o dec), and EtOAc/MeOH/*C6H6 (m 241-243o dec). Its solubility in MeCN is 1mg/mL.  D varies from -296o to -327o (c 0.2, MeOH). max (MeOH) 445, 240nm (log 4.43, 4.49), max (MeOH, 10N HCl, 1:1) 477nm (log 4.21) and max (MeOH, 0.1N NaOH) 458, 344, 285 (log 3.05, 4.28, 4.13). It is HIGHLY TOXIC, light sensitive and anti-neoplastic. [Bullock & Johnson, J Chem Soc 3280 1957, Beilstein 27 III/IV 9642.]
Incompatible with oxidizers (chlorates, nitrates, peroxides, permanganates, perchlorates, chlorine, bromine, fluorine, etc.); contact may cause fires or explosions. Keep away from alkaline materials, strong bases, strong acids, oxoacids, epoxides.
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- 13641685631 021-54285032