Daunorubicin
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| Clinical data | |
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| Trade names | Cerubidine, others |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a682289 |
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| Routes of administration | Intravenous |
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| Metabolism | Liver |
| Eliminationhalf-life | 26.7hours(metabolite) |
| Excretion | Bile ductand urinary |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.040.048 |
| Chemical and physical data | |
| Formula | C27H29NO10 |
| Molar mass | 527.526g·mol−1 |
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Daunorubicin,also known asdaunomycin,is achemotherapy medicationused to treatcancer.[2]Specifically it is used foracute myeloid leukemia(AML),acute lymphoblastic leukemia(ALL),chronic myelogenous leukemia(CML), andKaposi's sarcoma.[2]It is administered byinjection into a vein.[2]Aliposomalformulation known asliposomal daunorubicinalso exists.[2]
Common side effects include hair loss, vomiting,bone marrow suppression,and inflammation of the inside of the mouth.[2]Other severe side effects includeheart diseaseandtissue deathat the site of injection.[2]Use inpregnancymay harm the fetus.[2]Daunorubicin is in theanthracyclinefamily of medication.[3]It works in part by blocking the function oftopoisomerase II.[2]
Daunorubicin was approved for medical use in the United States in 1979.[2]It is on theWorld Health Organization's List of Essential Medicines.[4]It was originally isolated from bacteria of theStreptomycestype.[5]
Medical uses
[edit]It slows or stops the growth of cancer cells in the body. Treatment is usually performed together with other chemotherapy drugs (such ascytarabine), and its administration depends on the type of tumor and the degree of response.[citation needed]
In addition to its major use in treating acute myeloid leukemia, daunorubicin is also used to treatneuroblastoma.Daunorubicin has been used with other chemotherapy agents to treat the blastic phase ofchronic myelogenous leukemia.[citation needed]
Daunorubicin is also used as the starting material for semi-synthetic manufacturing ofdoxorubicin,epirubicinandidarubicin.[citation needed]
Mechanism of action
[edit]Similar todoxorubicin,daunorubicin interacts with DNA byintercalationand inhibition of macromolecularbiosynthesis.[6][7]This inhibits the progression of the enzymetopoisomerase II,which relaxes supercoils in DNA; without action of topoisomerase II, these DNA supercoils interfere intranscriptionof DNA. Daunorubicin stabilizes the topoisomerase II complex after it has broken the DNA chain for replication, preventing the DNA double helix from being resealed and thereby stopping the process ofreplication. On binding to DNA, daunomycinintercalates,with its daunosamine residue directed toward the minor groove. It has the highest preference for two adjacent G/Cbase pairsflanked on the 5' side by an A/T base pair. Crystallography shows that daunomycin induces a local unwinding angle of 8°, and other conformational disturbances of adjacent and second-neighbour base pairs.[8] It can also inducehistoneeviction fromchromatinuponintercalation.[9][10]
History
[edit]In the 1950s, anItalianresearch company,FarmitaliaResearch Laboratories, began an organized effort to isolate anticancer compounds from soil-basedmicrobes.A soil sample was isolated from the area surrounding theCastel del Monte,a 13th-century castle inApulia.A new strain ofStreptomyces peucetiuswhich produced a red pigment was isolated, and an antibiotic was produced from this bacterium that was found to have good activity againstmurinetumors. Since a group ofFrenchresearchers discovered the same compound at about the same time, the two teams named the compound daunorubicin, combining the nameDauni,a pre-Roman tribe that occupied the area of Italy where the compound was isolated, with the French word forruby,rubis,describing the color.[11][12][13]Clinical trials began in the 1960s, and the drug saw success in treating acute leukemia and lymphoma.
However, by 1967, it was recognized that daunorubicin could produce fatal cardiac toxicity.[14]
In 2015–16, a team atOhio State University"showed that, by carefully manipulating strands of viral DNA, an origami structure with complex folds can be created in just 10 minutes. Incredibly, these structures are only 100 nanometers across – that’s 1,000 times smaller than the width of a human hair. Small volumes of daunorubicin can be wrapped up in these minuscule pods, which can then be released into a leukemia cell-filled environment."[15][16][unreliable medical source?]
Route of administration
[edit]Daunorubicin should only be administered in a rapidintravenous infusion.It should not be administeredintramuscularlyorsubcutaneously,since it may cause extensive tissuenecrosis. It should also never be administeredintrathecally(into thespinal canal), as this will cause extensive damage to thenervous systemand may lead todeath.Daunorubicin has been used intravitreally (inside the eye) for the purposes of preventing proliferative vitreoretinopathy, a common complication following retinal detachment surgery, but has not been found to be effective and is not used for any other ophthalmic purposes at this time.[17]
References
[edit]- ^"Daunorubicin (Cerubidine) Use During Pregnancy".Drugs.com.19 September 2019.Retrieved15 August2020.
- ^abcdefghi"Daunorubicin hydrochloride".The American Society of Health-System Pharmacists.Archivedfrom the original on 8 January 2017.Retrieved8 December2016.
- ^British National Formulary: BNF 69(69th ed.). British Medical Association. 2015. pp. 581–583.ISBN9780857111562.
- ^World Health Organization(2019).World Health Organization model list of essential medicines: 21st list 2019.Geneva: World Health Organization.hdl:10665/325771.WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
- ^Lin GQ, You QD, Cheng JF (2011).Chiral Drugs: Chemistry and Biological Action.John Wiley & Sons. p. 120.ISBN9781118075630.Archivedfrom the original on 21 December 2016.
- ^Fornari FA, Randolph JK, Yalowich JC, Ritke MK, Gewirtz DA (April 1994). "Interference by doxorubicin with DNA unwinding in MCF-7 breast tumor cells".Molecular Pharmacology.45(4): 649–656.PMID8183243.
- ^Momparler RL, Karon M, Siegel SE, Avila F (August 1976)."Effect of adriamycin on DNA, RNA, and protein synthesis in cell-free systems and intact cells".Cancer Research.36(8): 2891–2895.PMID1277199.Archivedfrom the original on 5 February 2009.
- ^Quigley GJ, Wang AH, Ughetto G, van der Marel G, van Boom JH, Rich A (December 1980)."Molecular structure of an anticancer drug-DNA complex: daunomycin plus d(CpGpTpApCpG)".Proceedings of the National Academy of Sciences of the United States of America.77(12): 7204–7208.Bibcode:1980PNAS...77.7204Q.doi:10.1073/pnas.77.12.7204.PMC350470.PMID6938965.
- ^Pang B, Qiao X, Janssen L, Velds A, Groothuis T, Kerkhoven R, et al. (2013)."Drug-induced histone eviction from open chromatin contributes to the chemotherapeutic effects of doxorubicin".Nature Communications.4:1908.Bibcode:2013NatCo...4.1908P.doi:10.1038/ncomms2921.PMC3674280.PMID23715267.
- ^Pang B, de Jong J, Qiao X, Wessels LF, Neefjes J (July 2015). "Chemical profiling of the genome with anti-cancer drugs defines target specificities".Nature Chemical Biology.11(7): 472–480.doi:10.1038/nchembio.1811.PMID25961671.
- ^Weiss RB (December 1992). "The anthracyclines: will we ever find a better doxorubicin?".Seminars in Oncology.19(6): 670–686.PMID1462166.
- ^Baruffa G (1966). "Clinical trials in Plasmodium falciparum malaria with a long-acting sulphonamide".Transactions of the Royal Society of Tropical Medicine and Hygiene.60(2): 222–224.doi:10.1016/0035-9203(66)90030-7.PMID5332105.
- ^Camerino B, Palamidessi G (1960). "Derivati della parazina II. Sulfonamdopir" [Derivatives of parazine II. Sulfonamdopir].Gazzetta Chimica Italiana[Italian Chemical Journal] (in Italian).90:1802–1815.
- ^Tan C, Tasaka H, Yu KP, Murphy ML, Karnofsky DA (March 1967)."Daunomycin, an antitumor antibiotic, in the treatment of neoplastic disease. Clinical evaluation with special reference to childhood leukemia".Cancer.20(3): 333–353.doi:10.1002/1097-0142(1967)20:3<333::AID-CNCR2820200302>3.0.CO;2-K.PMID4290058.S2CID19272219.
- ^"Researchers kill drug-resistant leukemia cells using DNA Trojan horse attack".IFL Science. 25 February 2016.
- ^Halley PD, Lucas CR, McWilliams EM, Webber MJ, Patton RA, Kural C, et al. (January 2016)."Daunorubicin-Loaded DNA Origami Nanostructures Circumvent Drug-Resistance Mechanisms in a Leukemia Model".Small.12(3): 308–320.doi:10.1002/smll.201502118.PMC4879968.PMID26583570.
- ^Mortensen ME, Cecalupo AJ, Lo WD, Egorin MJ, Batley R (1992). "Inadvertent intrathecal injection of daunorubicin with fatal outcome".Medical and Pediatric Oncology.20(3): 249–253.doi:10.1002/mpo.2950200315.PMID1574039.
