Effects of sinefungin on growth and sterol composition of Leishmania promastigotes.

The S-adenosylmethionine analogue sinefungin was tested in vitro against promastigotes of various strains of Leishmania. The IC50 values for the Leishmania mexicana, Leishmania major, and Leishmania donovani strains used were of the order of 10 ng/ml but the Leishmania amazonensis strain tested was more resistant to the drug, the IC50 value being 6 micrograms/ml. Sterol profiles, in which 24-alkyl (C28) sterols predominated, were relatively unaffected by sinefungin. Incorporation of label derived from either [methyl-2H3]methionine or [methyl-14C]methionine into sterols was not appreciably affected by treatment at a growth-inhibiting concentration of sinefungin. It was concluded that sinefungin had only a limited effect on sterol production at the 24-transmethylation step and it is unlikely that this is the primary cause of cell death.