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 micrograms per ml; these effects are reverted by 100 microM of squalene, but not by 100 microM of cholesterol. Lovastatin at the same amounts inhibits [14C]acetate incorporatin into sterols, isolated either by digitonin precipitation or thin layer chromatography. At 50 micrograms 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.
Institute of Biochemistry, University of La Plata, Argentina.
M
M
Florin-Christensen
J
J
Florin-Christensen
C
C
Garin
E
E
Isola
R R
RR
Brenner
L
L
Rasmussen
D000085:Acetates / Q000378:metabolism; D000818:Animals; D002784:Cholesterol / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007700:Kinetics; D008148:Lovastatin / Q000494:pharmacology*; D013185:Squalene / Q000494:pharmacology; D013261:Sterols / Q000096:biosynthesis*; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism
D000085:Acetates; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D013261:Sterols; D013185:Squalene; D002784:Cholesterol; D008148:Lovastatin