Samvisterin, a new natural antiplasmodial betulin derivative from Uapaca paludosa (Euphorbiaceae)

Abstract

Ethnopharmacological relevance: Uapaca paludosa is used in African traditional medicine for the treatment of malaria. Materials and methods: A bioguided fractionation of U. paludosa trunk bark extracts was performed on the basis of their antiplasmodial activity against Plasmodium falciparum. Results: A new natural betulin derivative named samvisterin (2) was isolated. In addition, 12 already known compounds were isolated from U. paludosa and tested against P. falciparum: squalene (1); lupeol (3), betulonic acid methyl ester (4), β-sitosterol (5), stigmasterol (6), betulin (7), betulinic acid (8), pentadecanoic acid (9), palmitic acid (10), margaric acid (11), stearic acid (12), methyl palmitate (13). With the exception of betulinic acid, all were isolated for the first time from U. paludosa. Their chemical structures were established on the basis of spectroscopic analysis. The antiplasmodial activity of compounds 1-8 was confirmed on the chloroquine-resistant strain of P. falciparum, FcM29-Cameroon, with IC 50 values ranging from 0.7 μg/ml (for 1) to 30 μg/mL (for 3). The cytotoxicity of the fractions and isolated compounds was also determined on KB and Vero cell lines in order to determine the cytotoxicity/activity ratio of each one. Conclusions: The results obtained with samvisterin (2) show that this new compound is the most promising of the series, with a weak cytotoxicity leading to the best selectivity index values.