The novel oxygenated chalcone, 2,4-dimethoxy-4'-butoxychalcone, exhibits potent activity against human malaria parasite Plasmodium falciparum in vitro and rodent parasites Plasmodium berghei and Plasmodium yoelii in vivo.
Previous studies have shown that licochalcone A, an oxygenated chalcone, exhibits antileishmanial and antimalarial activities. The present study was designed to examine the antimalarial activity of an analog of licochalcone A, 2,4-dimethoxy-4'-butoxychalcone (2,4mbc). 2,4mbc inhibited the in vitro growth of both a chloroquine-susceptible (3D7) and a chloroquine-resistant (Dd2) strain of Plasmodium falciparum in a [3H]hypoxanthine uptake assay. The in vivo activity of 2,4mbc was tested in mice infected with Plasmodium berghei or Plasmodium yoelii and in rats infected with P. berghei. 2,4mbc administered either orally, intraperitoneally, or subcutaneously for 5 days protected the mice from otherwise lethal infections of these parasites. 2,4mbc administered orally for 5 days reduced parasitemia in the rats infected with P. berghei. These results demonstrate that 2,4mbc exhibits potent antimalarial activity and might be developed into a new antimalarial drug.
Chen
M
M
Centre for Medical Parasitology, Department of Clinical Microbiology, University Hospital of Copenhagen, Denmark.
Brøgger Christensen
S
S
Zhai
L
L
Rasmussen
M H
MH
Theander
T G
TG
Frøkjaer
S
S
Steffansen
B
B
Davidsen
J
J
Kharazmi
A
A
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D047188:Chalcones; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008288:Malaria / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects; D010962:Plasmodium berghei; D010963:Plasmodium falciparum / Q000187:drug effects*; D010967:Plasmodium yoelii; D051381:Rats; D017208:Rats, Wistar
C108857:2,4-dimethoxy-4'-butoxychalcone; D000962:Antimalarials; D047188:Chalcones; D002599:Chalcone