Mode of action of anti-malaria drugs
Quinine-related drugs
- Quinine
- Chloroquine
- Mefloquine
- Halofantrine
all have similar structures and therefore are suppoosed to have the similar mechanisms
of action. Often also a cross resistance of Plasmodium for more than one drug of
this class of drugs is reported.
Chloroquine is a lysosomotropic drug. It is a weak base, uncharged at neutral pH
while it carries a positive charge at acidic pH. Owing to this property chloroquine
is selectively accumulated inside lysosomes. The uncharged compound rapidly diffuses
through the plasma and lysosomal membranes, while once charged the compound becomes
trapped inside the acidic lysosomal compartment of the parasite. This may lead to
the generation of concentration gradient of several orders of magnitude.
The intracellular trophozoite feeds on the haemoglobin
of the red blood cell that serves as a source of amino acids. Digestion of the globin
protein takes place inside the Plasmodium lysosome resulting in the generation of
free haem (ferriprotoporphyrin IX, FP). The latter is insoluble and precipitates
in the form of a black malaria pigment inside the lysosomes. Chloroquine in the lysosome
interferes with pigment formation and the FP-chloroquine complex is highly toxic
to the parasite.
Click here to read about chloroquine resistance
Mode of action of anti-folate drugs
Antifolates
- Sulphadoxin
- Pyrimethamine
- Proguanil
These drugs interfere with the synthesis of folic
acid and by consequence with the synthesis of nucleotides required for DNA synthesis.
Other drugs
- Quinhaosu (artemisinine) and its derivatives possible acts by inducing
oxidant stress! The internal peroxide of the drug is essential for its activity.
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