Strychnogucines A and B, Two New Antiplasmodial Bisindole Alkaloids from Strychnos icaja

Abstract

A reinvestigation of Strychnos icaja roots has resulted in the isolation of two tertiary quasi-symmetric bisindole alkaloids named strychnogucines A (1) and B (2). Their structures were identified by means of spectroscopic data interpretation. Compound 2 was highly active in vitro and compound 1 moderately active against four strains of Plasmodium falciparum. Strychnogucine B (2) was more active against a chloroquine-resistant strain than against a chloroquine-sensitive one (best CI 50 , 80 nM against the W2 strain). In addition, this compound showed a selective antiplasmodial activity with 25-180 times greater toxicity toward P. falciparum, relative to cultured human cancer cells (KB) or human fibroblasts (WI38).

In vitro and in vivo antimalarial and cytotoxic activity of five plants used in congolese traditional medicine

“…This plant is well known in our lab and old samples, collected 50 years ago (Denoel et al, 1953), have been studied for antiplasmodial properties. Several bisindole alkaloids were isolated from this plant and showed a high antiplasmodial and antimalarial activity (Frederich et al, 2000;Frederich et al, 2001;Frederich et al, 1999;Philippe et al, 2007). This study confirmed the activity of this plant on fresh samples.…”

“…Strychnos icaja and the cytotoxicity of Physalis angulata extract were previously described and showed, in this last case, a SI between 4 and 5 (Frederich et al, 2000;Frederich et al, 2001;Zirihi et al, 2005). Anisopappus chinensis showed the higher SI for its methanolic and dichloromethane extracts, with values superior to 10.…”

Antiplasmodial activities of sesquiterpene lactone from Carpesium cernum

“…In the assays of antimalarial activity, artemisinin was used as the positive control. Tests for antimalarial activity were carried out as described earlier [13]. The results were expressed by the inhibitory concentrations 50% (IC 50 ) and 90% (IC 90 ), representing the concentration of drug that induced, respectively, a 50% and a 90% parasitemia decrease compared to control culture.…”

“…Compounds were identified using spectral data such as 1 H, 13 C, HMBC and COSY NMR spectra, as well as EI-MS spectra, and by direct comparison with published spectral data and structures. NMR spectra were recorded in CDCl 3 and/or acetoned6 using a Bruker AMX 400 MHz spectrophotometer.…”

Study of the interaction of antiplasmodial strychnine derivatives with the glycine receptor

“…This could lead to a convulsant effect, a potential deleterous side-effect that should be studied before using these compounds as antimalarial drugs. Cytotoxic activities on human cancer lines have been previously evaluated and the antiprotozoal selectivity index has indicated a good selectivity (Frederich, De Pauw et al, 2001), so that our major concern remains to check wether these alkaloids are devoid of strychnine-like properties.…”