Synergism in vitro of lovastatin and miconazole as anti-leishmanial agents.
The antifungal drug miconazole and the cholesterol-lowering agent lovastatin (mevinolin) were used in combination to assess their potency as anti-leishmanial agents. The drug combination was synergistic, being more potent in terms of inhibition of promastigote proliferation, macrophage infection and amastigote numbers. In promastigote cultures the effect was more marked in Leishmania amazonensis than L. donovani. Analysis of the sterol compositions of both promastigote and amastigote cultures revealed the inhibition of sterol 14 alpha-demethylation by miconazole and showed some apparent evidence of inhibition of sterol biosynthesis by lovastatin.
Haughan
P A
PA
Department of Biochemistry, University of Liverpool, U.K.
Chance
M L
ML
Goad
L J
LJ
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D007891:Leishmania / Q000187:drug effects* / Q000378:metabolism; D007893:Leishmania donovani / Q000187:drug effects / Q000378:metabolism; D007896:Leishmaniasis / Q000188:drug therapy; D007898:Leishmaniasis, Visceral / Q000188:drug therapy; D008148:Lovastatin / Q000494:pharmacology*; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008825:Miconazole / Q000494:pharmacology*; D013261:Sterols / Q000096:biosynthesis
D013261:Sterols; D008825:Miconazole; D008148:Lovastatin