Purine Analogues

Detailed article on purine analogues in medical treatment

Classification
External resources

Purine analogues are a class of antimetabolite drugs that mimic the structure of purines, which are essential components of nucleic acids. These compounds are primarily used in the treatment of various types of cancer and autoimmune diseases. By interfering with the synthesis and function of nucleic acids, purine analogues can inhibit the proliferation of rapidly dividing cells.

Mechanism of Action

Purine analogues exert their effects by mimicking the natural purines, adenine and guanine, which are necessary for the synthesis of DNA and RNA. These analogues are incorporated into nucleic acids, leading to faulty DNA and RNA synthesis, which ultimately results in cell death. Some purine analogues also inhibit enzymes involved in purine metabolism, further disrupting nucleic acid synthesis.

Common Purine Analogues

6-Mercaptopurine

6-Mercaptopurine (6-MP) is a purine analogue that is commonly used in the treatment of acute lymphoblastic leukemia (ALL). It is metabolized into active thioguanine nucleotides, which are incorporated into DNA and RNA, causing cytotoxicity.

Azathioprine

Azathioprine is a prodrug that is converted into 6-mercaptopurine in the body. It is used as an immunosuppressant in organ transplantation and in the treatment of autoimmune diseases such as rheumatoid arthritis and Crohn's disease.

Fludarabine

Fludarabine is used primarily in the treatment of chronic lymphocytic leukemia (CLL). It is phosphorylated to its active triphosphate form, which inhibits DNA polymerase and ribonucleotide reductase, leading to apoptosis of cancer cells.

Cladribine

Cladribine is used in the treatment of hairy cell leukemia and multiple sclerosis. It is incorporated into DNA, causing strand breaks and apoptosis.

Clinical Uses

Purine analogues are used in various clinical settings, primarily for their antineoplastic and immunosuppressive properties. They are integral in the treatment regimens for certain leukemias and lymphomas, as well as in the management of autoimmune conditions.

Side Effects

The use of purine analogues can lead to several side effects, including myelosuppression, hepatotoxicity, and increased risk of infections due to immunosuppression. Monitoring of blood counts and liver function tests is essential during treatment.

Resistance

Resistance to purine analogues can occur through various mechanisms, such as increased drug efflux, decreased drug activation, or increased degradation of active metabolites. Understanding these mechanisms is crucial for developing strategies to overcome resistance.

Also see

• Antimetabolite
• Nucleic acid metabolism
• Chemotherapy
• Immunosuppressive drug