Synthesis and in vitro antimalarial activity of tetraoxane-amine/amide conjugates

A series of tetraoxanes, tetraoxane-amine and tetraoxane-amide conjugates have been synthesized and screened for in vitro antimalarial activity against chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum. Most of the conjugates showed slightly better antimalarial activity than the parent tetraoxanes. Three of the conjugate compounds were potentially active with IC50 values in the range of 0.38-0.80 mu M. Cytotoxicity of four selected compounds was also evaluated in a panel of four cancer (SK-MEL, KB, BT-549, SK-OV-3) and two non-cancer (Vero and LLC-PK11) cell lines up to a concentration of 25 mu M and none of the compounds was found toxic to any of the cells. (C) 2011 Elsevier Masson SAS. All rights reserved.