title: Strategies to reverse drug resistance in malaria.
abstract: OBJECTIVE
  Despite the current success of artemisinin combination therapy, the threat of drug-resistant falciparum malaria remains severe. Reversal of resistance to old drugs remains one strategy to deal with this problem. This review highlights recent significant findings.
  
  
  RESULTS
  This review provides a brief description of current antimalarials, their known or putative targets and mechanisms of resistance (where applicable). The main focus is recent reports on chloroquine resistance-reversing agents, including primaquine, so-called 'reversed chloroquines', novel resistance reversers such as xanthenes and two new mefloquine resistance-reversing compounds. A number of patents also report interesting new chloroquine resistance reversers, most notably HIV protease inhibitors. The review is confined to Plasmodium falciparum.
  
  
  CONCLUSIONS
  Only chlorpheniramine has so far shown some clinical utility as a chloroquine resistance reverser. Recent observations, however, that both primaquine and HIV protease inhibitors are chloroquine resistance reversers may eventually prove to be of clinical significance. 'Reversed chloroquines' are a scientifically innovative new class of antimalarial that both kill malaria parasites and have the potential to reverse resistance to their own antimalarial pharmacophore.
authors.affiliation: Department of Chemistry, University of Cape Town, South Africa. Timothy.Egan@uct.ac.za
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Egan
authors.forename: Catherine H
authors.initials: CH
authors.lastname: Kaschula
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004351:Drug Resistance; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics
chemical_list: D000962:Antimalarials