Lysosomes ph and the antimalarial action of chloroquine

Discussion in 'Canadian Drugs' started by alisarus, 25-Feb-2020.

  1. alexf2000 XenForo Moderator

    Lysosomes ph and the antimalarial action of chloroquine


    For decades, the drug was a front-line treatment and prophylactic for malaria. In a three-page paper published Tuesday in Cell Research, scientists at the Wuhan Institute of Virology’s State Key Laboratory of Virology write that both chloroquine and the antiviral remdesivir were, individually, “highly effective” at inhibiting replication of the novel coronavirus in cell culture.

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    Although the precise mechanism underlying the antimalarial effects of chloroquine remains unknown, chloroquine seems to exert its effects through the weak-base lysosome-tropic feature. When chloroquine enters the lysosome, it becomes protonated because of the low pH within the lysosome, and accumulation of the protonated form of chloroquine within the lysosome leads to less acidic conditions and, thereby, decreased lysosomal function. The primary discovery at this point was chloroquine’s mechanism of action the compound readily crossed the lysosomal membrane and became protonated, causing its accumulation within the lysosome. Chloroquine’s continued sequestration caused a significant increase in the lysosome’s pH, inactivating acid hydrolase enzymes and rendering the lysosome nonfunctional 22–24. In the case of malaria, in which parasites hijack the lysosomal system within red blood cells to provide a. Lysosomes and drug resistance in malaria. The introduction of chloroquine for malaria in the late 1940s was a great advance on quinine and mepacrine. It was cheap, non-toxic, and soon became the mainstay of therapy and prevention. For 10 years it was used successfully throughout the tropics.

    “It’s interesting in that it really lacks a lot of details but, nevertheless, if you look at the data as presented, at least in vitro, it seems like chloroquine can be used as an early-stage drug,” he said. Their drug screen evaluated five other drugs that were not effective. Though the paper is brief, John Lednicky, a professor at the University of Florida’s Emerging Pathogens Institute, found its results intriguing.

    Lysosomes ph and the antimalarial action of chloroquine

    Chloroquine Side Effects Common, Severe, Long Term -, Leaving the lysosome behind novel developments in.

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  7. Jan 23, 2017 Chloroquine analog is a diprotic weak base. The unprotonated form of chloroquine diffuses spontaneously and rapidly across the membranes of cells and organelles to acidic cytoplasmic vesicles such as endosomes, lysosomes, or Golgi vesicles and thereby increases their pH Al‐Bari 2015.

    • Targeting endosomal acidification by chloroquine analogs as a..
    • Lysosomes and drug resistance in malaria - The Lancet.
    • Chloroquine inhibits autophagic flux by decreasing..

    Apart from its well-known antimalarial effects, the drug has interesting biochemical properties that might be applied against some viral infections. Chloroquine exerts direct antiviral effects, inhibiting pH-dependent steps of the replication of several viruses including members of the flaviviruses, retroviruses, and coronaviruses. Mechanism of Action Chloroquine, a 4-aminoquinoline, is an anti-protozoal agent. The precise mechanism by which Chloroquine exhibits activity is not known. Chloroquine, may exert its effect against Plasmodium species by concentrating in the acid vesicles of the parasite and by inhibiting polymerization of heme. It can also inhibit certain enzymes by its interaction with DNA. Chloroquine and ammonium chloride, by virtue of their basic properties, have been shown to raise endocytic and lysosomal pH and thereby interfere with normal iron metabolism in a variety of cell types, including mononuclear phagocytes. Cellular iron metabolism is of critical importance to Legionella pneumophila.

     
  8. alexxxxxei Moderator

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  9. budulay Guest

    Allergic reaction to plaquenil DailyStrength I had been taking plaquenil since April for my lupus and sjogrens. It was working really well and just recently my rheumy told that I was in remission. I felt great. Then I had an allergic reaction to the plaquenil - a rash all over my body, neck, arms and legs. I stopped taking it 1 week ago.

    Treating Lupus with Anti-Malarial Drugs Johns Hopkins Lupus.