4-aminoquinoline

A class of compounds used in the treatment of malaria and other diseases

4-Aminoquinoline is a class of compounds that are derivatives of quinoline with an amino group at the 4-position. These compounds are primarily known for their use as antimalarial drugs. The most notable member of this class is chloroquine, which has been widely used in the treatment and prevention of malaria.

Chemical Structure

4-Aminoquinolines are characterized by the presence of a quinoline core, which is a heterocyclic aromatic organic compound, with an amino group (-NH₂) attached to the fourth carbon of the quinoline ring. This structural modification is crucial for their biological activity.

Mechanism of Action

The antimalarial activity of 4-aminoquinolines is primarily due to their ability to interfere with the Plasmodium parasite's ability to detoxify heme, a byproduct of hemoglobin digestion. In the acidic environment of the parasite's food vacuole, 4-aminoquinolines bind to heme, preventing its conversion to non-toxic hemozoin, thereby leading to the accumulation of toxic heme and subsequent parasite death.

Uses

4-Aminoquinolines are used in the treatment of:

• Malaria: Chloroquine and hydroxychloroquine are used to treat and prevent malaria caused by Plasmodium vivax, Plasmodium ovale, and Plasmodium malariae.
• Rheumatoid arthritis and lupus erythematosus: Hydroxychloroquine is also used as a disease-modifying antirheumatic drug (DMARD).

Resistance

Resistance to 4-aminoquinolines, particularly chloroquine, has become widespread in many parts of the world, especially in regions where Plasmodium falciparum is prevalent. This resistance is primarily due to mutations in the parasite's chloroquine resistance transporter (PfCRT) gene, which reduces the drug's accumulation in the parasite's food vacuole.

Safety and Side Effects

While generally well-tolerated, 4-aminoquinolines can cause side effects, including:

• Gastrointestinal disturbances
• Headache
• Dizziness
• Retinopathy (with long-term use)

Also see

• Quinoline
• Antimalarial drugs
• Chloroquine
• Hydroxychloroquine
• Plasmodium