INHIBITION OF TRYPANOSOMA-CRUZI GROWTH AND STEROL BIOSYNTHESIS BY LOVASTATIN

We have studied the effects of lovastatin, an inhibitor of hydroxy-methylglutaryl-CoA-reductase, on cultures of Trypanosoma cruzi epimastigotes. It inhibits growth at 10 and 30 μg per ml; these effects are reverted by 100μM of squalene, but not by 100 μM of cholesterol. Lovastatin at the same amounts inhibits [14C]acetate incorporatin into sterols, isolated either by digitonin precipitation or thin layer chromatography. At 50 μg per ml it kills most of the trypanosomes. These concentrations are below reported toxic levels for mammals; this drug and its analogs should, therefore, be tested as chemotherapeutic agents against Chagas' disease. © 1990.