Figure 8.3 Some alkaloids isolated from C. sanguinolenta.


11-hydroxycryptolepine Cryptospirolepine

Figure 8.3 Some alkaloids isolated from C. sanguinolenta.

8.5.1 In vitro Antiplasmodial Activity

The most studied of the C. sanguinolenta alkaloids is cryptolepine. Wright et al. (2001), using the lactate dehydrogenase assay described by Makler et al. (1993), found that the alkaloid had potent in vitro activity (IC50 = 0.44 mM) against Plasmodium falciparum (multi-drug-resistant strain K1). In the same system, chloroquine diphosphate had comparable activity (IC50 = 0.18mM). Against the chloroquine-sensitive strain HB3, the IC50 values for cryptolepine and chloroquine were 0.27 and 0.023 mM respectively. However, quindoline was found to be inactive in vitro (IC50 > 100 mM against K1 parasites. This was thought to be an indication that the N-methyl group in cryptolepine was necessary for antiplasmodial activity.

In an earlier in vitro study, IC50 values of 0.56 and 0.20 mM, respectively, were recorded for cryptolepine and chloroquine against chloroquine-resistant (FcB1) strains of P. falciparum (Grellier et al., 1996).

Cimanga et al. (1997) have also reported appreciable activity for 11-hydroxycryptolepine in vitro. Tests conducted recently, however, found this compound inactive in vitro (Wright, 2002).

The activities of various alkaloids extracted from C. sanguinolenta collected in Guinea Bissau have been screened in vitro against P. falciparum, strain K1, and the chloroqine-sensitive strain T996 (Paulo et al., 2000). Cryptolepine was found to be the most active (IC50 values of 0.23 and 0.059 mM against K1 and T996 strains, respectively). IC50 values of 0.26 mM (K1) and 0.019 mM (T996) were quoted for chloroquine. Other alkaloids tested were cryptoheptine (with IC50 values against K1 and T996 strains of 0.8 and 1.2 mW, respectively) and cryptolepinoic acid (no significant activity). Paulo and associates inferred from the results that cryptolepine was cross-resistant with chloroquine. In the report by Wright et al. (2001), however, this relationship was not evident.

Kirby et al. (1995) found cryptolepine as active against the K1 strains of P. falciparum as chloroquine (IC50 = 0.11 and 0.20 yM, respectively).

Eight naturally occurring anhydronium bases have been tested in vitro against the K1 strain of P. falciparum (Wright et al., 1996). Cryptolepine showed activity (IC50 = 0.114 yM) similar to that of chloroquine (IC50 = 0.20 yM).

C. sanguinolenta root extract was 1 of 20 plant extracts tested by Tona et al. (1999) against P. falciparum in vitro. At 6 yg/ml this extract was reported to inhibit more than 60% parasite growth.

8.5.2 In vivo Antimalarial Activity

Given orally at 50 mg/kg/day for 4 days to Plasmodium berghei-infected mice, cryptolepine suppressed parasitaemia by 80.5%. Chloroquine diphosphate (at 5 mg/kg/day) lowered parasitaemia by 93.5% in the same model (Wright et al., 1996). However, no effect was observed when the alkaloid was administered subcutaneously at 113 mg/kg/day (Kirby et al., 1995).

Grellier et al. (1996) found that a dose of 2.5 mg/kg/day for 4 days of cryptolepine given by the intraperitonial (i.p.) route reduced parasitaemia in Plasmodium vinckei petteri-infected mice by 80%. A similar level of activity was recorded for chloroquine administered at 1.5 mg/kg/day for 4 days by the same route.

However, when a group of P. berghei-infected mice were given 20 mg/kg/day of cryptolepine i.p., fatalities occurred on the second day (Wright et al., 2001).

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