In vitro and in vivo evaluation of betulinic acid as an antimalarial.
The lupane-type triterpene betulinic acid was isolated from an ethanol extract of the root bark of the Tanzanian tree Uapaca nitida Müll-Arg. (Euphorbiaceae). The in vitro antiplasmodial IC50 values of betulinic acid against chloroquine resistant (K1) and sensitive (T9-96) Plasmodium falciparum were found to be 19.6 micrograms/mL and 25.9 micrograms/mL, respectively. The in vitro activities of several related triterpenes were also evaluated. Betulin was found to be inactive at 500 micrograms/mL for both K1 and T9-96. Ursolic acid exhibited IC50 values of 36.5 micrograms/mL and 28 micrograms/mL, and oleanolic acid exhibited IC50 values of 88.8 micrograms/mL and 70.6 micrograms/mL against K1 and T9-96, respectively. When betulinic acid was tested for in vivo activity in a murine malaria model (P. berghei) the top dosage employed of 250 mg/kg/day was ineffective at reducing parasitaemia and exhibited some toxicity. Betulinic acid has not previously been evaluated for in vivo activity. This is believed to be the first compound to be isolated from U. nitida.
Steele
J C
JC
Jodrell Laboratory, Richmond, Surrey, UK.
Warhurst
D C
DC
Kirby
G C
GC
Simmonds
M S
MS
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D004195:Disease Models, Animal; D019665:Euphorbiaceae / Q000737:chemistry* / Q000627:therapeutic use; D008288:Malaria / Q000628:therapy*; D051379:Mice; D008826:Microbial Sensitivity Tests; D009828:Oleanolic Acid / Q000737:chemistry / Q000494:pharmacology; D053978:Pentacyclic Triterpenes; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry; D010962:Plasmodium berghei / Q000187:drug effects*; D010963:Plasmodium falciparum / Q000187:drug effects*; D011897:Random Allocation; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000094062:Betulinic Acid; D000097245:Ursolic Acid
D000962:Antimalarials; D009828:Oleanolic Acid; D053978:Pentacyclic Triterpenes; D010936:Plant Extracts; D014315:Triterpenes; D000094062:Betulinic Acid; D000097245:Ursolic Acid