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 Trypanosoma brucei brucei trypomastigotes. The most active compounds against L. donovani promastigotes were 7beta-aminomethylcholesterol and 7alpha,beta-aminocholesterol (IC50 in a range from 1 to 3 microM, pentamidine: 2.8 microM). These compounds were active on intramacrophage amastigotes with IC50 of 1.3 microM. Such an activity justifies further in vivo antileishmanial evaluation. Against T. b. brucei, (24R,S)-24-hydroxy-24-methylcholesterol (MEC, 12.5 microM) was the most active compound from these series.
Bazin
Marc-Antoine
MA
Centre d'Etudes et de Recherche sur le Médicament de Normandie, UFR des Sciences Pharmaceutiques, 5, rue Vaubénard, 14032 Caen cedex, France.
Loiseau
Philippe M
PM
Bories
Christian
C
Letourneux
Yves
Y
Rault
Sylvain
S
El Kihel
Laïla
L
D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002478:Cells, Cultured; D005260:Female; D007893:Leishmania donovani / Q000145:classification / Q000187:drug effects*; D008264:Macrophages / Q000469:parasitology; D051379:Mice; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D013237:Stereoisomerism; D013256:Steroids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014346:Trypanosoma brucei brucei / Q000187:drug effects*
D000981:Antiprotozoal Agents; D013256:Steroids; D014344:Trypanocidal Agents