Strategies to reverse drug resistance in malaria
- 1 December 2007
- journal article
- review article
- Published by Ovid Technologies (Wolters Kluwer Health) in Current Opinion in Infectious Diseases
- Vol. 20 (6), 598-604
- https://doi.org/10.1097/qco.0b013e3282f1673a
Abstract
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. 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. 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.Keywords
This publication has 37 references indexed in Scilit:
- Is PfCRT a channel or a carrier? Two competing models explaining chloroquine resistance in Plasmodium falciparumTrends in Parasitology, 2007
- Antimalarial drugs inhibiting hemozoin (β-hematin) formation: A mechanistic updateLife Sciences, 2007
- Mutations in transmembrane domains 1, 4 and 9 of the Plasmodium falciparum chloroquine resistance transporter alter susceptibility to chloroquine, quinine and quinidineMolecular Microbiology, 2006
- Re-evaluation of how artemisinins work in light of emerging evidence of in vitro resistanceTrends in Molecular Medicine, 2006
- Chemosensitizers in Drug Transport Mechanisms Involved in Protozoan ResistanceCurrent Drug Targets - Infectious Disorders, 2005
- A critical role for PfCRT K76T in Plasmodium falciparum verapamil-reversible chloroquine resistanceThe EMBO Journal, 2005
- pfmdr1 GENOTYPING AND IN VIVO MEFLOQUINE RESISTANCE ON THE THAI-MYANMAR BORDERThe American Journal of Tropical Medicine and Hygiene, 2005
- Defining the role of PfCRT in Plasmodium falciparum chloroquine resistanceMolecular Microbiology, 2005
- Chloroquine Resistance in Plasmodium falciparum Malaria Parasites Conferred by pfcrt MutationsScience, 2002
- Chloroquine resistance not linked to mdr-like genes in a Plasmodium falciparum crossNature, 1990