Antiplasmodial activity of Cryptolepis sanguinolenta alkaloids from leavesand roots

The roots of Cryptolepis sanguinolenta have been investigated for their che mical composition since 1931 but so far no studies on the leaves have been reported although they are used in traditional medicine in Guinea-Bissau. T wo new alkaloids identified as cryptolepinoic acid (1) and methyl cryptolep inoate (2) and the known alkaloids cryptolepine (4), hydroxycryptolepine (5 /5a) and quindoline (6), were isolated from the ethanolic and chloroformic leaf extracts. Aqueous and ethanolic extracts of the leaves and roots and s even alkaloids isolated from those extracts were tested in vitro against Pl asmodium falciparum K1 (multidrug-resistant strain) and T996 (chloroquine-s ensitive clone). All the extracts were shown to give 90% inhibition of P. f alciparum K1 growth at concentrations <23 mu g/ml. Cryptolepine (4) was the most active alkaloid tested with IC50 values (0.23 mu M to K1; 0.059 mu M to T996) comparable with chloroquine (0.26 mu M to K1; 0.019 mu M to T996). The indolobenzazepine alkaloid cryptoheptine (7) was the second most activ e with IC50 values of 0.8 mu M (K1) and 1.2 mu M (T996). Cryptolepinoic aci d (1) showed no significant activity while its ethyl ester derivative 3 was active against P. falciparum K1 (IC50 = 3.7 mu M). All the indoloquinoline alkaloids showed cross-resistance with chloroquine but not the indolobenza zepine alkaloid 7. It was noticed that alkaloids with weakly basic characte ristics were active whereas other structurally related alkaloids with diffe rent acid-base profiles were inactive. These observations are in agreement with the antimalarial mechanism of action for quinolines.