Synthesis of oxysterols and nitrogenous sterols with antileishmanial and trypanocidal activities

Two sterol families have been synthesized: the first one is nitrogenous sterols containing amino, N-hydroxyimino or cyano group and the second one is oxysterols such as ketosterol and hydroxysterols. These compounds were then evaluated in vitro against Leishmania donovani promastigotes and Thypanosoma brucei brucei trypomastigotes. The most active compounds against L. donovani promastigotes were 7 beta-aminomethylcholesterol and 7 alpha,beta-aminocholesterol (IC50 in a range from 1 to 3 mu M, pentamidine: 2.8 mu M). These compounds were active on intramacrophage amastigotes with IC50 of 1.3 mu M. Such an activity justifies further in vivo antileishmanial evaluation. Against T. b. brucei, (24R, S)-24-hydroxy-24-methyl cholesterol (MEC, 12.5 mu M) was the most active compound from these series. (c) 2006 Published by Elsevier Masson SAS.