Antimalarial alkaloid from Hypoestes forskaolii

Following on from previous studies, we brought further our quest for anti-malarial agents isolated from plants grown in the Saudi Arabian Peninsula. Methanolic extracts were prepared from eighteen Saudi plants and then tested in vitro to assess their anti-malarial effects on Plasmodium falciparum K1, (a chloroquine-resistant strain) as well as their cytotoxicity on MRC5 (human diploid embryonic lung cell line) cells. Moderate anti-malarial activity was observed in extracts prepared from Hypoestes forskaolii (Vahl) R. Br. (IC₅₀ value of 5.5 μg/ml) and Rhus retinorrhaea (IC₅₀: 7.71 μg/ml). The remaining sixteen plant extracts appeared to be inactive (IC₅₀ > 12.5 μg/ml). A novel phenanthro-quinolizidine alkaloid, 15β-hydroxycryptopleurine-N-oxide, was isolated from H. forskaolii using bio-guided fractionation procedures. Chloroquine-resistant (K1) and chloroquine-sensitive (FCR3) strains of P. falciparum appeared very sensitive to the anti-malarial activity of 15β-hydroxycryptopleurine-N-oxide, giving IC₅₀ of 6.11 and 5.13 nM respectively. It showed cytotoxicity against MRC5 "IC₅₀ of 24.45 nM" with selectivity indices of 4.0 and 4.76 against K1 and FCR3 strains, respectively. It is our understanding that this is the first account on phenanthro-quinolizidine alkaloids anti-malarial activity on a chloroquine-resistant P. falciparum strain.