What Is Chloroquine?
Chloroquine (chemical formula: C18H26ClN3) is an aminoquinoline derivative first developed in the 1940s for the treatment of malaria. It is also known as aralen and acts specifically against Plasmodium falciparum. Its therapeutic effect is achieved by interfering with the Plasmodium falciparum’s DNA synthesis.
At room temperature, chloroquine is a white crystalline substance soluble in water. It is odorless and has a bitter taste. Chloroquine is alkaline in environments below pH 8.5 and is basic in environments above pH 8.5.
There are two commercially available chloroquines: chloroquine phosphate and hydroxychloroquine. Hydroxychloroquine, a derivative of chloroquine with a hydroxyl group (-OH) attached to the end of the side chain, is often used because it is more rapidly absorbed through the digestive tract and is less toxic than chloroquine.
Uses of Chloroquine
Chloroquine is primarily used in the pharmaceutical field as an antimalarial agent. It is developed based on the structure of quinine, another antimalarial drug, and is said to be significantly more effective than quinine.
Chloroquine is particularly effective against strains of Plasmodium falciparum that are resistant to other antimalarial drugs. However, the mechanism of action of chloroquine in autoimmune diseases is not fully understood, and research is ongoing in this area.
Properties of Chloroquine
Chloroquine is a white crystalline powder with a bitter taste and is odorless. It is virtually insoluble in water, but its solubility increases under acidic conditions. It is readily soluble in alcohol and organic solvents like acetone. Chloroquine has a melting point above 250°C and a boiling point of about 455°C. It is basic with a pKa of 8.4.
Chloroquine is relatively unstable to light and is subject to degradation by light and oxidants. It also has drug-drug interactions that require caution during clinical use. For example, antacids that inhibit gastric acid secretion may decrease the absorption rate of chloroquine, and ampicillin may decrease blood levels when combined with chloroquine.
Chloroquine is rapidly absorbed from the intestine, and side effects and symptoms of over-inoculation generally appear within an hour. The risk of death from overdose is estimated to be about 20%, with symptoms including drowsiness, visual changes, seizures, respiratory arrest, ventricular fibrillation, and hypotension. In addition to human use, chloroquine has been widely used for protozoan infections in aquariums and chicken malaria on farms.
Structure of Chloroquine
Chloroquine is a basic organic compound with the chemical formula C18H26ClN3 and a molecular weight of 319.9 g/mol. The drug was developed through structural optimization based on quinacrine, the original structure of which is quinine.
Chloroquine reacts with acids like hydrochloric acid and sulfuric acid to form salts. When marketed as a drug, the hydrochloride or phosphate salt is generally used. Since it has no optical isomers, it has a single molecular structure.
The structure of chloroquine can be determined by various analytical techniques, including ultraviolet and infrared spectroscopy.
Other Information on Chloroquine
Chloroquine Production Methods
Several industrial methods exist for the production of chloroquine. For instance, the manufacturing process of chloroquine phosphate includes the following steps:
- Treating quinoline with thionyl chloride to obtain 4-chloroquinoline, which is then further chlorinated with chlorine gas to 4,7-dichloroquinoline.
- Condensing 1-diethylamino-4-aminopentane under heating conditions to obtain chloroquine.
- Reacting the resulting chloroquine with phosphoric acid to obtain chloroquine phosphate, which has excellent storage stability.