Destruction of Leishmania mexicana amazonensis amastigotes by leucine methyl ester: protection by other amino acid esters.
L-Amino acid esters, such as leucine methyl ester (Leu-OMe) can destroy intracellular as well as isolated amastigotes of Leishmania mexicana amazonensis by a mechanism which may involve ester hydrolysis by parasite enzymes. We show here that several other esters prevented the killing of the amastigotes by Leu-OMe. Destruction of Leishmania within macrophages in culture was assessed microscopically and viability of isolated parasites was monitored by reduction of the tetrazolium MTT. The main features of the protective effect were similar for intracellular and for isolated amastigotes. Thus, (i) effective prevention of parasite killing required that the protective ester be present in the medium prior to and during exposure of infected cells or parasites to Leu-OMe; (ii) the same esters protected intracellular and isolated Leishmania against damage by Leu-OMe. Ranks of protective activity, as determined on isolated amastigotes were: Gly-OBz greater than Tyr-OMe greater than Ile-OMe greater than Met-OMe greater than Val-OMe greater than Ala-OMe greater than Gly-OMe greater than D-Leu-OMe; (iii) several esters were inactive in both systems (Leu-OBz, Trp-OMe and Phe-OMe). Protective activity was associated with leishmanicidal (e.g. Gly-OBz, Tyr-OMe) as well as with non-leishmanicidal (e.g. Ile-OMe, Val-OMe) esters. The results are compatible with the hypothesis that protective esters inhibit the activity of parasite enzyme(s) which hydrolyse Leu-OMe.
Alfieri
S C
SC
Unité d'Immunophysiologie Cellulaire, Institut Pasteur, Paris, France.
Zilberfarb
V
V
Rabinovitch
M
M
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D004952:Esters; D007532:Isoleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007894:Leishmania mexicana / Q000187:drug effects*; D007930:Leucine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008264:Macrophages / Q000469:parasitology
D000596:Amino Acids; D004952:Esters; D007532:Isoleucine; C053773:isoleucine methyl ester; C030365:leucine methyl ester; D007930:Leucine