Polymorphism in plasmodium falciparum drug transporter proteins and reversal of in vitro chloroquine resistance by a 9,10-dihydroethanoanthracene derivative.
BG958 reverses resistance in chloroquine-resistant isolates from different countries. Five mutations in the Plasmodium falciparum crt (pfcrt) gene resulting in the amino acid changes K76T, M74I, N75E, A220S, and R371I are systematically identified in resistance-reversed Asian, African, and Brazilian parasites which possess the pfcrt (CIET) haplotype. In combination with BG958, the activity of chloroquine is increased in parasites with the N86Y mutation in pfmdr1.
Millet
Julie
J
Unité de Parasitologie, Institut de Médecine Tropicale du Service de Santé Armées, Marseille, France
Alibert
Sandrine
S
Torrentino-Madamet
Marylin
M
Rogier
Christophe
C
Santelli-Rouvier
Christiane
C
Bigot
Patricia
P
Mosnier
Joel
J
Baret
Eric
E
Barbe
Jacques
J
Parzy
Daniel
D
Pradines
Bruno
B
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology*; D000962:Antimalarials / Q000494:pharmacology*; D002352:Carrier Proteins / Q000235:genetics*; D002738:Chloroquine / Q000494:pharmacology*; D016054:DNA, Protozoan / Q000235:genetics / Q000302:isolation & purification; D004351:Drug Resistance; D004357:Drug Synergism; D019450:Genes, MDR / Q000235:genetics; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins; D009154:Mutation / Q000235:genetics; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000235:genetics*; D015800:Protozoan Proteins; D016053:RNA, Protozoan / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000873:Anthracenes; D000962:Antimalarials; C495224:BG 958; D002352:Carrier Proteins; D016054:DNA, Protozoan; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D016053:RNA, Protozoan; D002738:Chloroquine