Format

Send to:

Choose Destination
See comment in PubMed Commons below
Antimicrob Agents Chemother. 2012 May;56(5):2283-9. doi: 10.1128/AAC.00166-12. Epub 2012 Feb 21.

Saquinavir inhibits the malaria parasite's chloroquine resistance transporter.

Author information

  • 1Research School of Biology, The Australian National University, Canberra, ACT, Australia. Rowena.Martin@anu.edu.au

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 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.

PMID:
22354298
[PubMed - indexed for MEDLINE]
PMCID:
PMC3346596
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk