Affiliation:
1. Institute of Medical Sciences, Department of Medicine
2. Tropical Disease Unit, Toronto General Hospital
3. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
Abstract
ABSTRACT
Quinoline resistance in malaria is frequently compared with P-glycoprotein-mediated multidrug resistance (
mdr
) in mammalian cells. We have previously reported that nonylphenolethoxylates, such as NP30, are potential
Plasmodium falciparum
P-glycoprotein substrates and drug efflux inhibitors. We used in vitro assays to compare the ability of verapamil and NP30 to sensitize two parasite isolates to four quinolines: chloroquine (CQ), mefloquine (MF), quinine (QN), and quinidine (QD). NP30 was able to sensitize (reversal, >80%)
P. falciparum
to MF, QN, QD, and, to a lesser extent, CQ. The presence of 2 μM verapamil had no effect on mefloquine resistance; however, the presence of verapamil modulated the activities of QN and QD in a manner parallel to that observed for CQ. Genetic analysis of putative quinoline resistance genes did not suggest an association between known point mutations in
pfcrt
and
pfmdr1
and NP30 sensitization activity. We conclude that the sensitization action of NP30 is distinct both phenotypically and genotypically from that of verapamil.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
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