Chloroquine mainly acts on red stage schizonts, and after 48 to 72 hours, the schizonts in the blood are eliminated. This product is ineffective against the infrared phase of vivax malaria, so it cannot eradicate vivax malaria. Falciparum malaria can be eradicated. Chloroquine has no effect on the infrared phase and has no direct effect on gametocytes, so it cannot be used to prevent the disease and interrupt the spread.
After the effect of chloroquine, the nucleus of the malaria parasite ruptured, the cytoplasm appeared vacuolated, and the malaria melanin accumulated into large masses. It is known that chloroquine cannot kill malaria parasites immediately, but it can affect its reproduction. This product has extremely strong binding to nuclear proteins. Because the negatively charged 7-chloro group on its quinoline ring is close to the 2-hydroxyl group on the guanine of DNA, chloroquine is inserted into the middle of the double helix structure of DNA. . Produces nitric oxide synthase with DNA, thereby blocking DNA copying and RNA gene expression.
Chloroquine can also inhibit the incorporation of ammonium sulfate into the DNA and RNA of Plasmodium, which affects the reproduction of Plasmodium because the production of nucleotides is reduced. Experiments using isotope-labeled chloroquine have confirmed that infected blood cells can accumulate a large amount of chloroquine, and the food vesicles and lysosomes of Plasmodium are where it is concentrated. The amount of chloroquine concentrated is related to the pH in the food bubble. The pH in the food bubble is acidic and alkaline (the suitable pH for dissolved hemoglobin concentration is 4), which can cause the concentration of the alkaline drug chloroquine, and the concentration of the drug is consumed. The hydroxide ions in the food bubble further increase the pH value in the food bubble, which damages the hemoglobin enzyme that absorbs hemoglobin. Plasmodium cannot digest the ingested hemoglobin, causing the growth and development of malaria parasites. Indispensable carbohydrates are lacking, causing DNA to dissolve. In addition, chloroquine can also affect the transfer of oleic acid into unsaturated fatty acids, control phosphate dehydrogenase and hexokinase, etc.
In recent years, some people believe that the initial effect of chloroquine on Plasmodium Huntsman dye is to cause the coagulation of malarial melanin. Ferroporphyrin IX (FP), the main component of malaria melanin, can damage blood cells and produce nitric oxide synthase with chloroquine to mediate the therapeutic effect of chloroquine. It is inferred that the body of the malaria parasite has one or more protein kinases, that is, “FP conjugate”, which may be a human albumin that can be fused with FP to produce non-toxic nitric oxide synthase, which makes the malaria parasite extracellular. The matrix is protected from FP hazards. The principle of action of chloroquine may be to separate the “FP conjugate” from FP and produce chloroquine-FP nitric oxide synthase with toxic side effects, thereby fully exerting its anti-malarial effect. Because of changes in protein kinases, chloroquine loses its required efficacy. This may be one of the reasons why malaria parasites are resistant to chloroquine.
