Diaminopyrimidines: Effects, Uses & Risks

The group of diaminopyrimidines includes various active ingredients that are used medically as antibiotics. They all have a similar negative effect on the growth of bacteria in the human body. Because of their low reactivity with human organs, they make excellent pharmaceuticals. Treatment results in rapid and complete healing of symptoms without significant side effects.

What are diaminopyrimidines?

Diaminopyrimidines are organic compounds of two amines (diamino) with a heterocyclic pyrimidine ring. The ring consists of four carbon atoms in which two nitrogen atoms are integrated. Depending on the position of the two amino groups, four different structures (isomers) result, which are designated according to the position of the amines: 2,4-diaminopyrimidine, 2,5-diaminopyrimidine, 4,5-diaminopyrimidine and 4,6-diaminopyrimidine. All four isomers are chemically identical, but have different reactivity to other compounds because of the different amine positions. The amino groups are very reactive (basic) towards acid compounds because of the hydrogen atoms. Diaminopyrimidines are the basis for many pharmaceuticals.

Pharmacological action

Diaminopyrimidines act as folic acid inhibitors. Folic acid (vitamin B9) is the cause of many harmful compounds. Folic acid also converts in the body to purines, which can crystallize. They can clog arteries and smaller organic channels. Folic acid is produced differently by cells depending on the species. In bacteria, it is reduced from dihydrofolate. In this process, tetrahydrofolic acid is formed. Diaminopyrimidines and their chemical derivatives interfere with this process by inhibiting the enzyme dihydrofolate reductase. They prevent the corresponding compounds from coupling to the enzyme. As a result, folic acid cannot be produced. This leads to a depletion of folic acid in the bacterial cell and ultimately to its death. The antibacterial effect reaches a wide range of pathogens, so diaminopyrimidines play an important role in the derivation of antibiotics. They are similar to sulfonamides in their action. The isomers form starting materials for derivatives and thus also inhibit antibiotic resistance in bacteria.

Medical application and use

Various diaminopyrimidine-based agents are used in medicine. There are monotherapeutics such as trimethoprim, which contains only diaminopyrimidine. But there are also combination solutions with sulfonamides such as cotrimoxazole. Physicians administer the two variants orally for bacterial control in urinary tract infections. The bacteria die after a short time (approximately 14 – 20 hours after ingestion) and are excreted from the body. Methotrexate is a derivative and is similar to folic acid. The bacterial cells incorporate this into the cells instead of folic acid, which also leads to the depletion of folic acid and the death of the same. It is used by physicians primarily in cancer therapy. Diaminopyrimidines have prevented cancer cells from spreading in clinical trials. Derivatives of these compounds are being tested but are not approved. In autoimmune disease, it is used as a suppressor, preventing an overreaction of the immune system. Iclaprim, another derivative, can probably be used for bacterial complaints of skin symptoms. It is currently in the approval process (as of 2016). Other derivatives of diaminopyrimidines are used in rheumatism therapy, but also against hair loss. The structurally similar diaminopyridines are used in the treatment of neurological diseases. In addition to their use as antibiotics, their efficacy against protozoa is also being tested. Protozoa, unlike bacteria, are eukaryotic. They have a nucleus, which bacteria do not have. Diaminopyrimidines can act directly in bacterial plasma, whereas in protozoa they must penetrate the nucleus itself. This complicates the efficacy of the active ingredients. However, clinical studies show positive results.

Risks and side effects

Folic acid formation is also important for the human body. Dihydrofolate reduction takes place in cells. However, treatment with diaminopyrimidine cannot harm the human body because of its specific effect on bacteria. The medication with diaminopyrimidines is probably not significant enough to lead to organic damage.Bacterial folic acid producers are more susceptible than organic production. Since the effect of diaminopyrimidine is limited to bacteria and protozoa, this results in high tolerability. Sporadic gastrointestinal symptoms or nausea may occur. Detection in blood plasma subsides after a few hours. The body excretes diaminopyrimidines after about 12-14 hours. No further side effects have occurred to date.