In vitro and in vivo evaluation of betulinic acid as an antimalarial

The lupane-type triterpene betulinic acid was isolated from an ethanol extr act of the root bark of the Tanzanian tree Uapaca nitida Mull-Arg, (Euphorb iaceae), 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 mu g/mL and 25.9 mu g/mL, respectively. The in vitro acti vities of several related triterpenes were also evaluated. Betuhn was found to be inactive at 500 mu g/mL for both K1 and T9-96, Ursolic acid exhibite d IC50 values of 36.5 mu g/mL and 28 mu g/mL, and oleanolic acid exhibited IC50 values of 88.8 mu g/mL and 70.6 mu g/mL against K1 and T9-96, respecti vely. When betulinic acid was tested for in vivo activity in a murine malar ia model (P. berghei) the top dosage employed of 250 mg/kg/day was ineffect ive at reducing parasitaemia and exhibited some toxicity. Betulinic acid ha s not previously been evaluated for in vivo activity. This is believed to b e the first compound to be isolated from U. nitida. Copyright (C) 1999 John Whey & Sons, Ltd.