Doxorubicin hydrochloride
[CAS# 25316-40-9]

Identification

• Classification: API >> Antineoplastic agents >> Antibiotic antineoplastic agents
• Name: Doxorubicin hydrochloride
• Synonyms: (8S-cis)-10-[(3-Amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8,9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxynaphthacene-5,12-dione hydrochloride
• Molecular Formula: C₂₇H₂₉NO₁₁.HCl
• Molecular Weight: 579.99
• CAS Registry Number: 25316-40-9
• EC Number: 246-818-3
• SMILES: C[C@H]1[C@H]([C@H](C[C@@H](O1)O[C@H]2C[C@@](CC3=C2C(=C4C(=C3O)C(=O)C5=C(C4=O)C(=CC=C5)OC)O)(C(=O)CO)O)N)O.Cl

Properties

• Solubility: 50 mM (H2O), 50 mM (DMSO) (Expl.)
• Melting point: 216 °C (decomp.) (Expl.)

Safety Data

• Hazard Symbols: GHS07;GHS08 Dander
• Risk Statements: H302-H315-H319-H340-H350-H360
• Safety Statements: P203-P264-P264+P265-P270-P280-P301+P317-P302+P352-P305+P351+P338-P318-P321-P330-P332+P317-P337+P317-P362+P364-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Carcinogenicity	Carc.	1B	H350
Acute toxicity	Acute Tox.	4	H302
Eye irritation	Eye Irrit.	2	H319
Germ cell mutagenicity	Muta.	1B	H340
Reproductive toxicity	Repr.	1B	H360
Skin irritation	Skin Irrit.	2	H315
Reproductive toxicity	Repr.	2	H361
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H411
Serious eye damage	Eye Dam.	1	H318
Germ cell mutagenicity	Muta.	1A	H340
Carcinogenicity	Carc.	1A	H350
Specific target organ toxicity - repeated exposure	STOT RE	2	H373
Specific target organ toxicity - single exposure	STOT SE	3	H335
Acute toxicity	Acute Tox.	4	H312
Eye irritation	Eye Irrit.	2A	H319
Carcinogenicity	Carc.	2	H351
Acute toxicity	Acute Tox.	4	H332

Discovery and Applications

Doxorubicin hydrochloride is a widely used chemotherapeutic agent that belongs to the anthracycline class of drugs. It is primarily used in the treatment of various cancers, including breast cancer, ovarian cancer, lung cancer, and leukemia. Doxorubicin works by intercalating into DNA strands, disrupting DNA replication and transcription, which ultimately leads to cell death. It also generates free radicals that cause further cellular damage. Due to its potent anticancer properties, doxorubicin has become one of the cornerstone drugs in chemotherapy regimens for a variety of malignancies.

The discovery of doxorubicin dates back to the 1950s, when it was isolated from *Streptomyces peucetius*, a bacterium found in soil. Initially, researchers were investigating microbial sources of potential anticancer agents, and the discovery of doxorubicin marked a significant breakthrough. The drug was first introduced to clinical use in the early 1970s, following extensive preclinical and clinical trials that demonstrated its efficacy against a wide range of cancers. It was marketed under the trade name Adriamycin and quickly gained recognition as an essential part of cancer chemotherapy.

Doxorubicin hydrochloride has been used in the treatment of both solid tumors and hematologic cancers. In breast cancer, for example, it is often used as part of combination chemotherapy regimens like AC (doxorubicin and cyclophosphamide) or FAC (fluorouracil, doxorubicin, and cyclophosphamide). It is also used to treat various leukemias, lymphomas, and sarcomas. The drug is typically administered intravenously, although it may also be given by other routes depending on the type of cancer being treated.

One of the challenges in the use of doxorubicin is its potential for causing significant side effects. These include cardiotoxicity, which can lead to long-term heart damage, as well as nausea, vomiting, hair loss, and myelosuppression, which affects the bone marrow’s ability to produce blood cells. The cardiotoxicity associated with doxorubicin is dose-dependent, and the cumulative dose over time can increase the risk of heart failure. As a result, patients receiving doxorubicin are closely monitored for signs of heart damage, and the drug's dosage is adjusted to minimize these risks. To mitigate cardiotoxicity, doxorubicin is often used in combination with other drugs that protect the heart, such as dexrazoxane, which reduces the drug’s harmful effects on heart tissue.

Doxorubicin has also inspired the development of liposomal formulations, which aim to reduce its toxicity while maintaining its efficacy. Liposomal doxorubicin, such as the product Doxil, is encapsulated in lipid-based nanoparticles, which allow for targeted drug delivery to cancer cells. This formulation helps to reduce the incidence of side effects, such as hair loss and cardiotoxicity, by limiting the exposure of healthy tissues to the drug. Liposomal doxorubicin is particularly useful in the treatment of ovarian cancer and Kaposi’s sarcoma.

Despite its side effects, doxorubicin remains an essential and highly effective chemotherapeutic agent. Researchers continue to explore ways to improve its delivery, reduce its toxicities, and enhance its anticancer activity. The use of doxorubicin in combination with other drugs, as well as the development of new formulations and drug delivery systems, holds promise for improving cancer treatment outcomes in the future.

In conclusion, doxorubicin hydrochloride is a crucial drug in the treatment of various cancers. Its discovery from microbial sources revolutionized cancer chemotherapy, and its potent anticancer effects have made it a standard treatment option for many malignancies. While its use is associated with significant side effects, including cardiotoxicity, ongoing research continues to enhance its clinical application, making it a cornerstone in the fight against cancer.

References

1979. Angioneurotic Edema from Doxorubicin. The New England Journal of Medicine, 301(7).
DOI: 10.1056/NEJM197908163010719

1979. EFFICACY OF DOXORUBICIN IN PROLYMPHOCYTIC LEUKAEMIA. British Journal of Haematology, 42(3).
DOI: 10.1111/j.1365-2141.1979.tb01158.x

1979. A clinical-pharmacological evaluation of hepatic arterial infusion of adriamycin. Cancer Research, 39(10).
URL: https://pubmed.ncbi.nlm.nih.gov/476647