INVITRO ANTIMALARIAL AND CYTOTOXIC ACTIVITIES OF SEMISYNTHETIC DERIVATIVES OF BRUSATOL

Brusatol 2a was converted to the amide 2d, then the hydroxyl function on ring A of both compounds was acylated by a lipidic alpha-amino acid to give compounds 2b and 2e. To assess the effect of the size of the alkyl side chain on the biological activity the acetate 2c was also produced. The acylated brusatol derivatives 2b and 2c had the same in vitro antimalarial activity as brusatol 2a but both compounds were significantly less cytotoxic in vitro against KB tumour cells. The conversion of the C-13 ester group of brusatol to an amide group (2d) significantly decreased the antimalarial activity which was further reduced upon A-ring acylation by a lipidic alpha-amino acid (2e).