Antimetabolites are a class of chemotherapy drugs that interfere with the synthesis of DNA,

the genetic material that controls cell growth and division. They work by mimicking the structure
of essential molecules that cells need to make DNA, such as folate, purines, and pyrimidines.
When antimetabolites are incorporated into DNA, they disrupt the normal DNA replication
process, preventing cells from dividing and ultimately leading to cell death.

Mechanism of Action

Antimetabolites can act at different stages of DNA synthesis, including:

● Nucleotide synthesis: Antimetabolites can mimic the structure of nucleotides, the

building blocks of DNA. When incorporated into DNA, they can cause errors in DNA
replication, leading to mutations and cell death.
● Folate metabolism: Folate is a vitamin that is essential for DNA synthesis.
Antimetabolites like methotrexate inhibit the enzyme that converts folic acid to its active
form, tetrahydrofolate (THF). This disruption in folate metabolism prevents cells from
making DNA and leads to cell death.
● Purine biosynthesis: Purines are nitrogenous bases that are also essential for DNA
synthesis. Antimetabolites like mercaptopurine and thioguanine mimic the structure of
purines and compete with them for incorporation into DNA. This disruption in purine
synthesis prevents cells from making DNA and leads to cell death.
● Pyrimidine biosynthesis: Pyrimidines are nitrogenous bases that are also essential for
DNA synthesis. Antimetabolites like fluorouracil (5-FU) mimic the structure of pyrimidines
and compete with them for incorporation into DNA. This disruption in pyrimidine synthesis
prevents cells from making DNA and leads to cell death.

Types of Antimetabolites

There are many different types of antimetabolites, each with its own specific mechanism of
action and target. Some of the most common antimetabolites include:

● Methotrexate: Used to treat a variety of cancers, including leukemia, lymphoma, and

breast cancer
● Mercaptopurine: Used to treat leukemia and other blood cancers
● Thioguanine: Used to treat acute myeloid leukemia (AML)
● 5-FU (fluorouracil): Used to treat a variety of cancers, including colorectal cancer, breast
cancer, and head and neck cancer
● Cytarabine (Ara-C): Used to treat acute myeloid leukemia (AML)

Applications of Antimetabolites

Antimetabolites are a versatile class of chemotherapy drugs that are used to treat a wide range
of cancers. They are particularly effective against cancers that rapidly divide, such as leukemias
and lymphomas. Antimetabolites can be used alone or in combination with other chemotherapy
drugs or radiation therapy.

Side Effects of Antimetabolites

Antimetabolites can cause a variety of side effects, including:

● Myelosuppression: Antimetabolites can suppress the production of blood cells, leading to

anemia, leukopenia, and thrombocytopenia.
● Gastrointestinal (GI) toxicity: Antimetabolites can cause nausea, vomiting, diarrhea, and
mouth sores.
● Liver toxicity: Antimetabolites can damage the liver, causing jaundice and elevated liver
enzymes.
● Neurotoxicity: Antimetabolites can damage the nervous system, causing tingling,
numbness, and weakness.
● Hair loss: Antimetabolites can cause hair loss, which is usually temporary.

Despite their side effects, antimetabolites are valuable tools in the treatment of cancer.
They are often effective in controlling cancer growth and prolonging survival.