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Saquinavir inhibits the malaria parasite's chloroquine resistance transporter.
- Source :
-
Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2012 May; Vol. 56 (5), pp. 2283-9. Date of Electronic Publication: 2012 Feb 21. - Publication Year :
- 2012
-
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.
- Subjects :
- Animals
Antimalarials pharmacology
Biological Transport drug effects
Drug Combinations
Drug Synergism
Female
HIV Protease Inhibitors pharmacology
Humans
Lopinavir pharmacology
Malaria, Falciparum parasitology
Membrane Transport Proteins genetics
Membrane Transport Proteins metabolism
Mutation
Oocytes cytology
Oocytes metabolism
Plasmodium falciparum genetics
Plasmodium falciparum metabolism
Protozoan Proteins genetics
Protozoan Proteins metabolism
Ritonavir pharmacology
Saquinavir pharmacology
Tritium
Xenopus laevis
Chloroquine pharmacology
Malaria, Falciparum drug therapy
Oocytes drug effects
Plasmodium falciparum drug effects
Protozoan Proteins antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1098-6596
- Volume :
- 56
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Antimicrobial agents and chemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 22354298
- Full Text :
- https://doi.org/10.1128/AAC.00166-12