From the Guidelines
An antimetabolite is a chemical substance that interferes with normal cellular metabolism by mimicking essential metabolites, thereby blocking enzymes involved in cellular processes. These compounds are used in medicine, particularly in cancer treatment, as they can target rapidly dividing cells by preventing DNA replication and cell division. According to 1, antimetabolites such as capecitabine and gemcitabine are included among preferred first-line single agents for breast cancer treatment. The mechanism of action of antimetabolites involves mimicking natural metabolites like nucleotides, amino acids, or vitamins, allowing them to be incorporated into cellular components but preventing normal metabolic processes from occurring. Common antimetabolites used in medicine include methotrexate, 5-fluorouracil, and 6-mercaptopurine, which have applications in treating various cancers and autoimmune disorders due to their immunosuppressive properties. As noted in 1, older-generation antimetabolites like aminopterin and methotrexate have pronounced teratogenic and abortive potential, highlighting the need for careful consideration in their use, especially during pregnancy. Key characteristics of antimetabolites include:
- Interference with normal cellular metabolism
- Mimicry of essential metabolites
- Inhibition of enzymes involved in cellular processes
- Targeting of rapidly dividing cells
- Applications in cancer treatment and autoimmune disorders. Overall, antimetabolites play a crucial role in medicine, particularly in oncology, due to their ability to exploit subtle differences between normal and pathological cellular processes.
From the Research
Definition of Antimetabolite
- Antimetabolites are defined as interfering with the synthesis of the DNA constituents 2
- They are structural analogues, either of purine and pyrimidine bases (or the corresponding nucleosides), or of folate cofactors, which are involved at several steps of purine and pyrimidine biosynthesis 2
- Their first mechanism of action is to induce depletion in nucleotides, inducing in turn an inhibition of DNA replication 2
- Some antimetabolites are able to get inserted fraudulently into nucleic acids, inducing structural abnormalities leading to cell death by other mechanisms, including DNA breaks 2
Examples of Antimetabolites
- Methotrexate (MTX) 3, 4, 5, 6
- 5-fluorouracil (5-FU) 3, 4, 5, 6
- Ara-C (arabinosylcytosine) 3, 6
- 6-mercaptopurine (6-MP) 3, 4, 6
- Fludarabine 4
- Gemcitabine 4
Mechanism of Action
- Antimetabolites interfere with the synthesis of DNA constituents, leading to inhibition of DNA replication and cell death 2
- They can also induce structural abnormalities in nucleic acids, leading to cell death by other mechanisms, including DNA breaks 2
- The combination of antimetabolites with other anticancer agents can enhance their therapeutic efficacy 4, 6