Daunorubicin hydrochloride CAS 23541-50-6
Introduction：Basic information about Daunorubicin hydrochloride CAS 23541-50-6, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Daunorubicin hydrochloride Basic information
| Product Name: | Daunorubicin hydrochloride |
| Synonyms: | 5,12-Naphthacenedione,8-acetyl-10-[(3-aMino-2,3,6-trideoxy-a-L-lyxo-hexopyranosyl)oxy]-7,8,9,10-tetrahydro-6,8,11-trihydroxy-1-Methoxy-,hydrochloride (1:1), (8S,10S)-;daunoblastin;daunoblastina;daunomycinchlorohydrate;ndc0082-4155;ondena;rp13057hydrochloride;rubidomycinhydrochloride |
| CAS: | 23541-50-6 |
| MF: | C27H29NO10.ClH |
| MW: | 563.98 |
| EINECS: | 245-723-4 |
| Product Categories: | Antitumour;Carbohydrates & Derivatives;Chiral Reagents;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;API;Anti-cancer&immunity;Coronavirus |
| Mol File: | 23541-50-6.mol |
Daunorubicin hydrochloride Chemical Properties
| Melting point | 190°C (dec) |
| alpha | D20 +248 ±5° (c = 0.05-0.1 in methanol) |
| storage temp. | Inert atmosphere,2-8°C |
| solubility | Freely soluble in water and in methanol, slightly soluble in alcohol, practically insoluble in acetone. |
| form | solid |
| color | red to deep red |
| Water Solubility | Soluble in water (50 mM) |
| λmax | 477nm(H2O)(lit.) |
| Sensitive | Hygroscopic |
| Merck | 14,2832 |
| BRN | 4229221 |
| Stability: | Stability |
| InChIKey | GUGHGUXZJWAIAS-SMLRDAARNA-N |
| SMILES | C1=CC2C(=O)C3=C(O)C4C[C@](C(C)=O)(O)C[C@H](O[C@@H]5O[C@@H](C)[C@@H](O)[C@@H](N)C5)C=4C(O)=C3C(=O)C=2C(OC)=C1.Cl |&1:10,16,18,20,22,24,r| |
| EPA Substance Registry System | Daunorubicin hydrochloride (23541-50-6) |
Safety Information
| Hazard Codes | Xn,Xi |
| Risk Statements | 22-40-42/43-36/37/38-20/21/22 |
| Safety Statements | 22-36/37-45-37/39-36-26 |
| RIDADR | UN 2811 6.1/PG 3 |
| WGK Germany | 3 |
| RTECS | HB7878000 |
| F | 3-10 |
| HazardClass | 6.1(b) |
| PackingGroup | III |
| HS Code | 29419059 |
| Storage Class | 6.1C - Combustible acute toxic Cat.3 toxic compounds or compounds which causing chronic effects |
| Hazard Classifications | Acute Tox. 3 Oral Carc. 2 Muta. 2 Repr. 1B |
| Toxicity | LD50 in mice (mg/kg): 26 i.v. (DiMarco, 1969) |
| Description | Daunorubicin HCl (23541-50-6) is an antitumor antibiotic used in the treatment of acute myeloid leukemias.1?Induces DNA damage by intercalation.2?Induces apoptosis in a variety of cell lines.3?Inhibition of autophagy with chloroquine enhances daunorubicin-induced apoptosis in K562 cells.4?Cell permeable. |
| Chemical Properties | Dark Red Crystals |
| Originator | Cerubidine,Rhone-Poulenc Rorer,France |
| Uses | Antineoplastic;DNA intercaling |
| Uses | anti-neoplastic LD50 in mice 26 mg/kg |
| Uses | A DNA intercalator which may suppress acute leukemia proliferation |
| Uses | Anthracycline antibiotic related to the rhodomycins. Antineoplastic |
| Definition | ChEBI: Daunorubicin hydrochloride is an anthracycline. |
| Manufacturing Process | A 170 liter fermentation vessel is charged with: Corn steep 2.400 kg Sucrose 3.600 kg Calcium carbonate 0.900 kg Ammonium sulphate 0.240 kg Water to 100 liters This culture medium has a pH of 6.15. It is sterilised by passage of steam at122°C for 40 minutes. After cooling, the volume of the broth is 120 liters andthe pH is 7.20. The medium is then seeded with 200 cc of a culture of thestrain Streptomyces 31723. The culture is carried out for 27 hours at 26°-27°C with agitation and aeration with sterile air. It is then suitable for seedingthe production culture. The production culture is carried out in an 800 literformentation vessel charged with the following: Soya flour 20 kg Distillers' solubles 2.500 kg Soya oil 2.500 liters Soya oil 2.500 liters Sodium chloride 5 kg Water to 465 liters Starch 10 kg The pH of the medium thus obtained is adjusted to 7.20 with concentratedsodium hydroxide solution (400 cc). The medium is then sterilised by thepassage of steam at 122°C for 40 minutes. After cooling, the volume of thebroth is 500 liters and the pH is 6.75. It is then seeded with 50 liters of theculture from the 170 liter fermentation vessel. Culture is carried out at 28°Cfor 67 hours with agitation and aeration with sterile air. The pH of the mediumis then 7.40 and the volume of the fermentation culture is 520 liters. Thequantitiy of antibiotic present in the medium is 29 μ/cc. The above fermentation culture (520 liters; activity 29 μ/cc) is placed in avessel equipped with an agitator and the pH is adjusted to 1.8 with aconcentrated solution of oxalic acid. Agitation is carried out for one hour and afiltration adjuvant (20 kg) then added. The mixture is filtered on a filter-pressand the filter-cake washed with water (100 liters) acidified to pH 2 with oxalicacid. The filtrate (612 liters) is treated with concentrated sodium hydroxidesolution until the pH is 4.5. The filtrate is then passed through a columncontaining Amberlite IRC 50 in hydrogen form (20 liters; diameter of column15.2 cm, height of column 200 cm, height of resin at rest in column 110 cm).The filtrate passes through the bed of Amberlite from base to top at a rate of40 liters/hour. The column is then washed with water (100 liters) at a rate of50 liters/hour circulating from base to top and then with methanol (containing10% water; 75 liters) circulating from top to base at a rate of 50 liters/hour.The washings are discarded and the column is then eluted with a solutionhaving the following composition (per liter): The eluate (100 liters), which contains the major part of the antibiotic, isconcentrated under reduced pressure at 35°C to 10 liters. The concentrate isextracted at pH 7.5 with chloroform (2 times 5 liters). The chloroformicextract is adjusted to pH 4 with a solution of acetic acid in chloroform (10:100by volume) and then concentrated at 30°C under reduced pressure to 100 cc.The antibiotic is precipitated by the addition of hexane (1 liter), separated,washed and dried to give an amorphous red powder (9 g) of activity 1,400μ/mg. The crude antibiotic (17.1 g) obtained as above described (activity 1530μ/mg) is dissolved with stirring in a mixture of methylene chloride (1.5 liters),carbon tetrachloride (0.3 liters) and water (1.8 liters). The pH is then adjusted 9865 RP (500 mg), obtained as above described, is dissolved in normalsulphuric acid (100 cc) and the solution obtained is heated for 20 minutes ona water-bath. After cooling and extracting with ethyl acetate (3 times 200 cc),the organic extract is dried over anhydrous sodium sulphate, filtered andconcentrated to a small volume, giving, after filtering, washing and drying,crystals (218.5 mg). These crystals (150 mg) are dissolved in chloroform (3cc) and benzene (1.5 cc) and the solution obtained is chromatographed on 20sheets of Arches No. 310 paper impregnated with a solution of acetonecontaining 20% formamide, and developed for 90 minutes by means of a 2:1mixture of chloroform and benzene saturatd with formamide. The principalzone of Rf = 0.86 is cut out of each of the 20 sheets and the 20 zones thuscut out are comminuted in a mixer in the presence of methanol. The mixtureobtained is filtered, concentrated, and water (10 volumes) added. Theprecipitate obtained is filtered off, washed and dried under reduced pressureto give crystals (120 mg). These crystals (170 mg) are dissolved in dioxancontaining 20% water (15 cc) and water acidified to pH 4 with 0.1 Nhydrochloric acid is added dropwise. The crystals formed are filtered off,washed and dried, thus giving the aglycone of 9865 RP (130 mg) in the formof orange-red needles, having a first melting point at 160°C and a second at225°C-230°C. Daudorubicin can be prepared by gene ingineering methods also.to 3 by the addition of normal hydrochloric acid (8 cc). After decanting, theaqueous phase is treated with methylene chloride (7 liters) and 0.1 N sodiumhydroxide solution (200 cc) to give a pH of 7.5. After decanting, the aqueousphase is again extracted at pH 7.5 with methylene chloride (3.5 liters). Themethylene chloride extracts are combined and concentrated to 100 cc. Afterthe addition of hexane (1 liter) to the concentrate, a product precipitates which is filtered off, washed and dried at 30°C under reduced pressure to givethe antibiotic 9865 RP (9.15 g) in the form of an amorphous orange-redpowder of activity 2180 μ/mg. |
| Brand name | Cerubidine (Bedford); Cerubidine (Sanofi Aventis); Cerubidine (Wyeth). |
| Therapeutic Function | Antineoplastic |
| General Description | Daunorubicin is available in 20- and 100-mg vials for reconstitution.The agent is given intravenously for the treatmentof acute nonlymphocytic and lymphocytic leukemia. Otherunlabeled uses include CML and Kaposi sarcoma. In general,its use is more limited than that of doxorubicin.Daunorubicin lacks the hydroxyl groups found at C-14 ofdoxorubicin. This leads to an increase in the amount of thealcohol metabolite daunorubicinol (active) arising as a resultof reduction of the side chain ketone. This, however, doesnot appear to lead to a significant increase in the occurrenceof cardiotoxicity compared with doxorubicin. The mechanismsof resistance and toxicities of daunorubicin are similarto that of doxorubicin; the major difference betweenthe two agents being the spectrum of cancers that they areused treat. A liposomal form of daunorubicin is also availableknown as DaunoXome. The drug offers the same advantagesas those seen for the liposomal form of doxorubicin. |
| General Description | Orange-red powder. Thin red needles decomposing at 188-190°C. An anti-cancer drug. |
| Air & Water Reactions | Water soluble. |
| Reactivity Profile | Daunorubicin hydrochloride may emit toxic oxides of nitrogen when heated. |
| Biological Activity | Anticancer agent that is clinically used to treat nonlymphocytic leukaemia. Inhibits RNA and DNA synthesis and causes DNA fragmentation in vivo . |
| Biochem/physiol Actions | Potent anticancer agent. Inhibits DNA and RNA synthesis as sequence specific ds-DNA intercalating agent. |
| Pharmacokinetics | Like Doxil (the liposomal formulation of doxorubicin), DaunoXome is indicated for use in AIDS-related Kaposi's sarcoma and is administered IV at a dose of 40 mg/m2 every 2 weeks. The pharmacokinetic profiles of Doxil and DaunoXome are similar. |
| Clinical Use | Daunorubicin is administered IV at a dose of 45 mg/m2 for the treatment of lymphocytic and nonlymphocytic leukemia. |
| Metabolism | The 18.5-hour terminal half-life of daunorubicin is approximately half that of doxorubicin, and the terminal half-life of the active daunorubicinol metabolite is 26.7 hours. Excretion is approximately 40% biliary and 25% urinary. |
| storage | +4°C |
| References | [1] GUY LAURENT J J. Signaling pathways activated by daunorubicin.[J]. Blood, 2001, 98 4 1: 913-924. DOI:10.1182/blood.v98.4.913 [2] FAN YANG . Doxorubicin, DNA torsion, and chromatin dynamics[J]. Biochimica et biophysica acta. Reviews on cancer, 2014, 1845 1: Pages 84-89. DOI:10.1016/j.bbcan.2013.12.002 [3] MICHÈLE MASQUELIER . Relationship between daunorubicin concentration and apoptosis induction in leukemic cells[J]. Biochemical pharmacology, 2004, 67 6: Pages 1047-1056. DOI:10.1016/j.bcp.2003.10.025 [4] WEIDONG HAN. Autophagy inhibition enhances daunorubicin-induced apoptosis in K562 cells.[J]. PLoS ONE, 2011: e28491. DOI:10.1371/journal.pone.0028491 |
Daunorubicin hydrochloride Preparation Products And Raw materials
| Raw materials | Starch-->AMBERLITE-->Sucrose-->SOYBEAN MEAL-->Soybean oil-->CORN STEEP LIQUOR-->N-[1-[4-(4-amino-5-hydroxy-6-methyl-oxan-2-yl)oxy-2,5,12-trihydroxy-7-methoxy-6,11-dioxo-3,4-dihydro-1H-tetracen-2-yl]ethylideneamino]-4-hydroxy-benzamide-->4-Hydroxybenzhydrazide |
| Preparation Products | ZORUBICIN HCL-->Doxorubicin hydrochloride |
