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.