What is the mechanism of action of chloroquine?
The major action of chloroquine is to inhibit the formation of hemozoin (Hz) from the heme released by the digestion of hemoglobin (Hb). The free heme then lyses membranes and leads to parasite death. Chloroquine resistance is due to a decreased accumulation of chloroquine in the food vacuole.
How does chloroquine work for malaria?
Chloroquine belongs to a group of medicines known as antimalarials. It works by preventing or treating malaria, a red blood cell infection transmitted by the bite of a mosquito.
What is the mechanism of action of antimalarial?
The quinoline-containing antimalarial drugs, chloroquine, quinine and mefloquine, are a vital part of our chemotherapeutic armoury against malaria. These drugs are thought to act by interfering with the digestion of haemoglobin in the blood stages of the malaria life cycle.
What is the mechanism of chloroquine resistance?
Resistance to chloroquine of malaria strains is known to be associated with a parasite protein named PfCRT, the mutated form of which is able to reduce chloroquine accumulation in the digestive vacuole of the pathogen.
What is hydroxychloroquine mechanism of action?
Chloroquine and hydroxychloroquine increase pH within intracellular vacuoles and alter processes such as protein degradation by acidic hydrolases in the lysosome, assembly of macromolecules in the endosomes, and posttranslation modification of proteins in the Golgi apparatus.
What is the mode of action for hydroxychloroquine?
An important mode of action of chloroquine and hydroxychloroquine is the interference of lysosomal activity and autophagy. It is widely accepted that chloroquine and hydroxychloroquine accumulate in lysosomes (lysosomotropism) and inhibit their function.
Is quinoline same as chloroquine?
Chloroquine (CQ) is a quinoline-based drug widely used for the prevention and treatment of malaria.
What is hydroxychloroquine mode of action?
What type of molecule is hydroxychloroquine?
It is an aminoquinoline, an organochlorine compound, a primary alcohol, a secondary amino compound and a tertiary amino compound. It derives from a chloroquine.
How does hydroxychloroquine work for SLE?
Hydroxychloroquine (HCQ) is an alkalinizing lysosomatropic drug that accumulates in lysosomes where it inhibits some important functions by increasing the pH. HCQ has proved to be effective in a number of autoimmune diseases including systemic lupus erythematosus (SLE).
How does [3H]chloroquine exert its antimalarial effect?
Chloroquine is thought to exert its antimalarial effect by preventing the polymerization of toxic heme released during proteolysis of hemoglobin in the Plasmodium digestive vacuole. The mechanism of this blockade has not been established. We incubated cultured parasites with subinhibitory doses of [3H]chloroquine and [3H] quinidine.
What is the role of chloroquine in the treatment of malaria?
Quinoline-containing antimalarial drugs, such as chloroquine, quinine and mefloquine, are mainstays of chemotherapy against malaria. The molecular basis of the action of these drugs is not completely understood, but they are thought to interfere with hemoglobin digestion in the blood stages of the m …
Do chloroquine and quinolines inhibit heme polymerase?
In this review the recent discovery that chloroquine and related quinolines inhibit the novel heme polymerase enzyme that is also present in the trophozoite food vacuole is introduced.
What chemicals are used to treat malaria?
Quinoline-containing antimalarial drugs, such as chloroquine, quinine and mefloquine, are mainstays of chemotherapy against malaria. The molecular basis of the action of these drugs is not completely understood, but they are thought to interfere with hemoglobin digestion in the blood stages of the malaria parasite’s life cycle.
Chloroquine inhibits the action of heme polymerase in malarial trophozoites, preventing the conversion of heme to hemazoin. 11, 15, 16 Plasmodium species continue to accumulate toxic heme, killing the parasite. 11
What is the half life of hydroxychloroquine and chloroquine?
Hydroxychloroquine and chloroquine are weak bases and have a characteristic ‘deep’ volume of distribution and a half-life of around 50 days.
How sensitive is heme polymerase to drug inhibition in chloroquine resistant trophozoites?
New data are also presented which show that heme polymerase isolated from chloroquine resistant trophozoites retains full sensitivity to drug inhibition, consistent with the observation that resistance involves a reduced accumulation of the drug at the (still vulnerable) target site.
How does chloroquine kill viruses?
Chloroquine passively diffuses through cell membranes and into endosomes, lysosomes, and Golgi vesicles; where it becomes protonated, trapping the chloroquine in the organelle and raising the surrounding pH. 10, 13 The raised pH in endosomes, prevent virus particles from utilizing their activity for fusion and entry into the cell. 14