title: 3-Halo Chloroquine Derivatives Overcome Plasmodium falciparum Chloroquine Resistance Transporter-Mediated Drug Resistance in P. falciparum.
abstract: Polymorphism in the Plasmodium falciparum chloroquine resistance transporter (PfCRT) was shown to cause chloroquine resistance. In this report, we examined the antimalarial potential of novel 3-halo chloroquine derivatives (3-chloro, 3-bromo, and 3-iodo) against chloroquine-susceptible and -resistant P. falciparum. All three derivatives inhibited the proliferation of P. falciparum; with 3-iodo chloroquine being most effective. Moreover, 3-iodo chloroquine was highly effective at potentiating and reversing chloroquine toxicity of drug-susceptible and -resistant P. falciparum.
authors.affiliation: Institute of Parasitology, McGill University, Ste. Anne de Bellevue, Quebec, Canada.
authors.forename: Sonia
authors.initials: S
authors.lastname: Edaye
authors.affiliation: Department of Chemistry, McGill University, Montreal, Quebec, Canada.
authors.forename: Dagobert
authors.initials: D
authors.lastname: Tazoo
authors.affiliation: Department of Chemistry, McGill University, Montreal, Quebec, Canada.
authors.forename: D Scott
authors.initials: DS
authors.lastname: Bohle
authors.affiliation: Institute of Parasitology, McGill University, Ste. Anne de Bellevue, Quebec, Canada Elias.Georges@McGill.CA.
authors.forename: Elias
authors.initials: E
authors.lastname: Georges
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis / Q000494:pharmacology*; D002738:Chloroquine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000187:drug effects* / Q000235:genetics; D015870:Gene Expression; D054879:Halogenation; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D000962:Antimalarials; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D002738:Chloroquine