Purine Antagonists

The purines (adenine and guanine) are chemicals used to build the nucleotides of DNA and RNA. The other class of base, the pyrimidines, are represented in DNA by thymine and cytosine and in RNA by cytosine and uracil.

Before a cell can divide it must duplicate its DNA content, so that each daughter cell has a complete and identical set of genetic information. The duplication process (replication) is like an assembly line, during which nucleotides are joined to each other to form the new DNA molecule. Phosphate groups and sugar molecules are joined together to create the long strands of DNA found in our chromosomes. The incorporation of a purine antagonist prevents the continued growth of the DNA and prevents cell division.⁽¹⁾

The purine antagonists function by inhibiting DNA synthesis in two different ways:

1. They can inhibit the production of the purine containing nucleotides, adenine and guanine. If a cell doesn't have sufficient amounts of purines, DNA synthesis is halted and the cell cannot divide.⁽¹⁾

2. They may be incorporated into the DNA molecule during DNA synthesis. The presence of the inhibitor is thought to interfere with further cell division.⁽¹⁾

Many times cancers become less sensitive, or resistant, to the drugs that are used to treat them. Learn about resistance to cancer drugs.

Some purine antagonists used to treat cancer:

• 6-Mercaptopurine
• Dacarbazine
• Fludarabine

A Closer Look at Purine Antimetabolites

One of the best known purine antimetabolite is acyclovir, an antiviral agent used to treat herpesvirus infections. Purine antagonists currently used to treat cancer patients include 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG). These drugs are similar to each other, and work in the same way. The structures the normal purines (adenine and guanine) with their antagonists (6-MP and 6-TG) are shown below.

 

1. Physician's Desk Reference, 56th ed., 2002. Medcial Economics: Thomson Healthcare.