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  • Saquinavir Inhibits the Malaria Parasite's Chloroquine Resistance Transporter

    Author(s)
    Martin, Rowena E
    Butterworth, Alice S
    Gardiner, Donald L
    Kirk, Kiaran
    McCarthy, James S
    Skinner-Adams, Tina S
    Griffith University Author(s)
    Skinner-Adams, Tina
    Year published
    2012
    Metadata
    Show full item record
    Abstract
    The antiretroviral protease inhibitors (APIs) ritonavir, saquinavir, and lopinavir, used to treat HIV infection, inhibit the growth of Plasmodium falciparum at clinically relevant concentrations. Moreover, it has been reported that these APIs potentiate the activity of chloroquine (CQ) against this parasite in vitro. The mechanism underlying this effect is not understood, but the degree of chemosensitization varies between the different APIs and, with the exception of ritonavir, appears to be dependent on the parasite exhibiting a CQ-resistant phenotype. Here we report a study of the role of the P. falciparum chloroquine ...
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    The antiretroviral protease inhibitors (APIs) ritonavir, saquinavir, and lopinavir, used to treat HIV infection, inhibit the growth of Plasmodium falciparum at clinically relevant concentrations. Moreover, it has been reported that these APIs potentiate the activity of chloroquine (CQ) against this parasite in vitro. The mechanism underlying this effect is not understood, but the degree of chemosensitization varies between the different APIs and, with the exception of ritonavir, appears to be dependent on the parasite exhibiting a CQ-resistant phenotype. Here we report a study of the role of the P. falciparum chloroquine resistance transporter (PfCRT) in the interaction between CQ and APIs, using transgenic parasites expressing different PfCRT alleles and using the Xenopus laevis oocyte system for the heterologous expression of PfCRT. Our data demonstrate that saquinavir behaves as a CQ resistance reverser and that this explains, at least in part, its ability to enhance the effects of CQ in CQ-resistant P. falciparum parasites.
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    Journal Title
    Antimicrobial agents and Chemotherapy
    Volume
    56
    Issue
    5
    DOI
    https://doi.org/10.1128/AAC.00166-12
    Subject
    Microbiology
    Medical microbiology
    Medical parasitology
    Pharmacology and pharmaceutical sciences
    Publication URI
    http://hdl.handle.net/10072/52083
    Collection
    • Journal articles

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