Synthesis of febrifuginol analogues and evaluation of their biological activities

A new series of febrifuginol analogues was prepared from L-glutamic acid. An antimalarial activity evaluation against chloroquine-sensitive (T96) and chloroquine-resistant (K1) Plasmodium falciparum indicated that all the tested compounds had very strong inhibitory activity. Compounds 4 and 17b' were inactive against KB, MCF7, HepG2 and LU1 cell lines even at a concentration of 100 mu M, while they exhibited significant inhibition towards P. falciparum. Comparison of the antimalarial activity and the cytotoxic properties revealed that the 2'S isomers were more active than the corresponding 2'R isomers for this series of febrifuginol analogues, indicating that the C-2' position is critical for the biological activity of this class of compounds. (C) 2014 Elsevier Ltd. All rights reserved.