Chloroquine is the drug of choice for preventing and treating acute forms of malaria caused by P. vivax, P. malariae, P. ovale, as well as sensitive forms of P. falciparum. The mechanism of its action is not completely clear, although there are several hypotheses explaining its antimalarial activity. Chloroquine and its analogs inhibit synthesis of nucleic acids of the parasite by affecting the matrix function of DNA. This happens by preliminary binding of the drug through hydrogen bonds with the purine fragments, and subsequent introduction of the chloroquine molecule between the orderly arranged base pairs into the spirals of the DNA of the parasite. Thus chloroquine prevents transcription and translation, which significantly limits the synthesis of DNA and RNA in the parasite. The selective toxicity of chloroquine in particular with respect to malarial plasmodia is also attributed to the ability of the parasitized red blood cells to concentrate the drug in amounts approximately 25 times greater than in normal erythrocytes. There is also a different hypothesis. Chloroquine has a high affinity for tissues of the parasite and is concentrated in its cytoplasm. As a weak base, it increases the pH of the intracellular lysosome and endosome. A more acidic medium in these organelles is needed for the parasite to affect mammalian cells. As a result, chloroquine inhibits growth and development of parasites.
Thus the main quality of chloroquine that exceeds all other antimalarial drug is its effect on erythrocytic schizonts (hematoschizotropic action). However, chloroquine also possesses amebicidal action. It has also been observed to have immunodepressive and antiarrhythmic properties.
It is used for all types of malaria, for chemotherapy, as well as for non-gastric amebia-sis, and amebic abscesses of the liver. Synonyms of this drug are nivaquine, quingamine, delagil, resoquine, atroquine, and others.
Hydroxychloroquine: Hydroxychloroquine, 7-chloro-4-[4-[ethyl(2-hydroxyethyl)amino]-1-methylbutylamino]quinoline (184.108.40.206), is made by a scheme similar to that of making chloroquine. Reacting 1-chloro-4-pentanone with 2-ethylaminoethanol gives the corresponding aminoketone (220.127.116.11), which undergoes reductive amination in conditions analogous to those described above, making 4-[ethyl(2-hydroxyethyl)amino]-1-methyl-butylamine (18.104.22.168). Reacting this with 4,7-dichlroquinoline (22.214.171.124) makes the desired hydroxychloroquine [10,11].
CH3-C-CH2-CH2-CH2-Cl + H-n( -- CH3-C-CH2-CH2-CH2 — n( '
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