Plasmodium berghei K173: selection of resistance to naphthoquine in a mouse model.
Naphthoquine (NQ), as a component of ARCO® which composed of NQ and artemisinin, is a new 4-aminoquinoline antimalarial synthesized by our institute. Here, a naphthoquine-resistant line of rodent malaria parasite was selected through exposing Plasmodium berghei Keyberg 173 strain to progressively increased drug pressure. The selected strain showed a more than 200-fold decreased susceptibility to NQ with a stable resistance phenotype after 10 serial passages without drug pressure or when cryopreserved over a period of 12 months. In a cross-resistance assay, the susceptibility of NQ-resistant parasites to chloroquine was decreased by 14.5-fold. These findings imply NQ-resistant parasites might be selected by long-term usage of NQ in epidemic areas and the efficacy of NQ or ARCO® in chloroquine-resistant Plasmodium falciparum epidemic areas should be monitored closely.
Wang
Hong
H
Department of Pharmacy, Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, 100071 Beijing, PR China.
Bei
Zhu-Chun
ZC
Wang
Jing-Yan
JY
Cao
Wu-Chun
WC
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000502:physiology; D004983:Ethanolamines / Q000494:pharmacology; D005449:Fluorenes / Q000494:pharmacology; D000078102:Lumefantrine; D008288:Malaria / Q000188:drug therapy / Q000469:parasitology; D008297:Male; D051379:Mice; D009285:Naphthoquinones / Q000494:pharmacology*; D010962:Plasmodium berghei / Q000187:drug effects*; D011739:Pyrimethamine / Q000494:pharmacology; D011897:Random Allocation
D000962:Antimalarials; D037621:Artemisinins; D004983:Ethanolamines; D005449:Fluorenes; D009285:Naphthoquinones; C543979:artemisinin-naphthoquine combination; D002738:Chloroquine; C031327:artemisinin; D000078102:Lumefantrine; D011739:Pyrimethamine