Daunorubicin
Encyclopedia
Daunorubicin or daunomycin (daunomycin cerubidine) is chemotherapeutic of the anthracycline
family that is given as a treatment for some types of cancer
. It is most commonly used to treat specific types of leukaemia (acute myeloid leukemia
and acute lymphocytic leukemia). It was initially isolated from Streptomyces peucetius.
A liposomal formulation of daunorubicin is marketed in the United States as DaunoXome.
research company, Farmitalia Research Laboratories, began an organized effort to isolate anticancer compounds from soil-based microbes. A soil sample was isolated from the area surrounding the Castel del Monte, a 13th century castle in Apulia
. A new strain of Streptomyces peucetius
which produced a red pigment was isolated, and an antibiotic was produced from this bacterium that was found to have good activity against murine tumor
s. Since a group of French
researchers discovered the same compound at about the same time, the two teams named the compound daunorubicin, combining the name Dauni, a pre-Roman tribe that occupied the area of Italy where the compound was isolated, with the French word for ruby
, rubis, describing the color. 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.
), and its administration depends on the type of tumor and the degree of response.
In addition to its major use in treating AML
, daunorubicin is also used to treat neuroblastoma
. Daunorubicin has been used with other chemotherapy agents to treat the blastic phase of chronic myelogenous leukemia
.
Daunorubicin is also used as the starting material for semi-synthetic manufacturing of doxorubicin
, epirubicin
and idarubicin
.
, with its daunosamine residue directed toward the minor groove. It has the highest preference for two adjacent G/C base pair
s flanked on the 5' side by an A/T base pair. Daunomycin effectively binds to every 3 base pairs and induces a local unwinding angle of 11o, but negligible distortion of helical conformation.
.
It should also never be administered intrathecal
ly (into the spinal canal
), as this will cause extensive damage to the nervous system
and may lead to death
.
Anthracycline
Anthracyclines are a class of drugs used in cancer chemotherapy derived from Streptomyces bacterium Streptomyces peucetius var...
family that is given as a treatment for some types of cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
. It is most commonly used to treat specific types of leukaemia (acute myeloid leukemia
Acute myeloid leukemia
Acute myeloid leukemia , also known as acute myelogenous leukemia, is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. AML is the most common acute...
and acute lymphocytic leukemia). It was initially isolated from Streptomyces peucetius.
A liposomal formulation of daunorubicin is marketed in the United States as DaunoXome.
History
In the 1950s, an ItalianItaly
Italy , officially the Italian Republic languages]] under the European Charter for Regional or Minority Languages. In each of these, Italy's official name is as follows:;;;;;;;;), is a unitary parliamentary republic in South-Central Europe. To the north it borders France, Switzerland, Austria and...
research company, Farmitalia Research Laboratories, began an organized effort to isolate anticancer compounds from soil-based microbes. A soil sample was isolated from the area surrounding the Castel del Monte, a 13th century castle in Apulia
Apulia
Apulia is a region in Southern Italy bordering the Adriatic Sea in the east, the Ionian Sea to the southeast, and the Strait of Òtranto and Gulf of Taranto in the south. Its most southern portion, known as Salento peninsula, forms a high heel on the "boot" of Italy. The region comprises , and...
. A new strain of Streptomyces peucetius
Streptomyces
Streptomyces is the largest genus of Actinobacteria and the type genus of the family Streptomycetaceae. Over 500 species of Streptomyces bacteria have been described. As with the other Actinobacteria, streptomycetes are gram-positive, and have genomes with high guanine and cytosine content...
which produced a red pigment was isolated, and an antibiotic was produced from this bacterium that was found to have good activity against murine tumor
Murinae
The Old World rats and mice, part of the subfamily Murinae in the family Muridae, comprise at least 519 species. This subfamily is larger than all mammal families except the Cricetidae and Muridae, and is larger than all mammal orders except the bats and the remainder of the...
s. Since a group of French
France
The French Republic , The French Republic , The French Republic , (commonly known as France , is a unitary semi-presidential republic in Western Europe with several overseas territories and islands located on other continents and in the Indian, Pacific, and Atlantic oceans. Metropolitan France...
researchers discovered the same compound at about the same time, the two teams named the compound daunorubicin, combining the name Dauni, a pre-Roman tribe that occupied the area of Italy where the compound was isolated, with the French word for ruby
Ruby
A ruby is a pink to blood-red colored gemstone, a variety of the mineral corundum . The red color is caused mainly by the presence of the element chromium. Its name comes from ruber, Latin for red. Other varieties of gem-quality corundum are called sapphires...
, rubis, describing the color. 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.
Uses
It slows or stops the growth of cancer cells in the body. Treatment is usually performed together with other chemotherapy drugs (such as cytarabineCytarabine
Cytarabine, or cytosine arabinoside, is a chemotherapy agent used mainly in the treatment of cancers of white blood cells such as acute myeloid leukemia and non-Hodgkin lymphoma. It is also known as Ara-C...
), and its administration depends on the type of tumor and the degree of response.
In addition to its major use in treating AML
Acute myeloid leukemia
Acute myeloid leukemia , also known as acute myelogenous leukemia, is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. AML is the most common acute...
, daunorubicin is also used to treat neuroblastoma
Neuroblastoma
Neuroblastoma is the most common extracranial solid cancer in childhood and the most common cancer in infancy, with an annual incidence of about 650 cases per year in the US , and 100 cases per year in the UK . Close to 50 percent of neuroblastoma cases occur in children younger than two years old...
. Daunorubicin has been used with other chemotherapy agents to treat the blastic phase of chronic myelogenous leukemia
Chronic myelogenous leukemia
Chronic myelogenous leukemia , also known as chronic granulocytic leukemia , is a cancer of the white blood cells. It is a form of leukemia characterized by the increased and unregulated growth of predominantly myeloid cells in the bone marrow and the accumulation of these cells in the blood...
.
Daunorubicin is also used as the starting material for semi-synthetic manufacturing of doxorubicin
Doxorubicin
Doxorubicin INN is a drug used in cancer chemotherapy. It is an anthracycline antibiotic, closely related to the natural product daunomycin, and like all anthracyclines, it works by intercalating DNA....
, epirubicin
Epirubicin
Epirubicin is an anthracycline drug used for chemotherapy. It is marketed by Pfizer under the trade name Ellence in the US and Pharmorubicin or Epirubicin Ebewe elsewhere....
and idarubicin
Idarubicin
Idarubicin or 4-demethoxydaunorubicin is an anthracycline antileukemic drug. It inserts itself into DNA and prevents DNA from unwinding by interfering with the enzyme topoisomerase II. It is an analog of daunorubicin, but the absence of a methoxy group increases its fat solubility and cellular...
.
Mode of action
On binding to DNA, daunomycin intercalatesIntercalation (chemistry)
In chemistry, intercalation is the reversible inclusion of a molecule between two other molecules . Examples include DNA intercalation and graphite intercalation compounds.- DNA intercalation :...
, with its daunosamine residue directed toward the minor groove. It has the highest preference for two adjacent G/C base pair
Base pair
In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a base pair...
s flanked on the 5' side by an A/T base pair. Daunomycin effectively binds to every 3 base pairs and induces a local unwinding angle of 11o, but negligible distortion of helical conformation.
Route of administration
Daunorubicin should only be administered in a rapid intravenous infusion. It should not be administered intramuscularly or subcutaneously, since it may cause extensive tissue necrosisNecrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
.
It should also never be administered intrathecal
Intrathecal
Intrathecal is an adjective that refers to something introduced into or occurring in the space under the arachnoid membrane of the brain or spinal cord...
ly (into the spinal canal
Spinal canal
The spinal canal is the space in vertebrae through which the spinal cord passes. It is a process of the dorsal human body cavity. This canal is enclosed within the vertebral foramen of the vertebrae...
), as this will cause extensive damage to the nervous system
Nervous system
The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous...
and may lead to death
Death
Death is the permanent termination of the biological functions that sustain a living organism. Phenomena which commonly bring about death include old age, predation, malnutrition, disease, and accidents or trauma resulting in terminal injury....
.