title: Dual-functioning antimalarials that inhibit the chloroquine-resistance transporter.
abstract: Malaria remains a major international health challenge. Resistance to a number of existing drugs and evidence of the emergence of artemisinin resistance has emphasized the need for new antimalarials. A new approach has been the preparation of dual-function compounds that include a chloroquine-like antimalarial group and a group that resembles a chloroquine chemosensitizer. This article reviews the recent discovery of such dual-function antimalarials that are proposed to target both hemozoin formation and the chloroquine resistance transporter, PfCRT. These are discussed in relation to the mechanism of action of 4-aminoquinolines, chloroquine resistance and resistance reversal.
authors.affiliation: Department of Chemistry, University of Cape Town, Private Bag, Rondebosch 7701, South Africa. timothy.egan@uct.ac.za
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Egan
authors.forename: David
authors.initials: D
authors.lastname: Kuter
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000962:Antimalarials; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D011804:Quinolines