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Destruction of intracellular and isolated Leishmania mexicana amazonensis amastigotes by amino acid amides

Published online by Cambridge University Press:  06 April 2009

M. Rabinovitch  and
V. Zilberfarb
M. Rabinovitch
Affiliation:
Unité d'Immunophysiologie Cellulaire, Institut Pasteur, and Centre National de la Recherche Scientifique (UA 04 1113), 25 Rue du Docteur Roux, 75724 Paris, France
V. Zilberfarb
Affiliation:
Unité d'Immunophysiologie Cellulaire, Institut Pasteur, and Centre National de la Recherche Scientifique (UA 04 1113), 25 Rue du Docteur Roux, 75724 Paris, France
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Summary

L-amino acid esters such as leucine methyl ester (Leu-OMe) destroy Leishmania mexicana amazonensis amastigotes by a mechanism which may involve hydrolysis of the compounds by parasite enzymes. Moreover, several esters (e.g. Ile-OMe) prevent the killing of parasites by Leu-OMe, perhaps by inhibition of the hydrolytic enzymes. We show here that certain amino acid amides are also leishmanicidal. Killing of Leishmania within macrophages was assessed microscopically, and that of isolated amastigotes was measured by reduction of the tetrazolium MTT. Amino acid amides were generally less active than the methyl esters and several were more toxic to the macrophages, as determined by inspection of Giemsa-stained preparations. Ranks of activity of the amides on isolated amastigotes were Trp > Leu > Phe > Met > Tyr. The amides of Ala, Gly, Val, Ile, His and D-Leu were inactive. This pattern of activity is similar to that of amino acid methyl esters. Ile-NH2 and a few other amides protected intracellular as well as isolated parasites from killing by Leu-OMe. Conversely, Ile-OMe reduced the toxicity of Leu-NH2 for isolated amastigotes. None of the esters or amides assayed prevented the destruction of Leishmania by Trp-NH2. The results are compatible with the view that amino acid esters and amides may be recognized by the same or similar parasite enzymes.

Type
Research Article
Information
Parasitology , Volume 96 , Issue 2 , April 1988 , pp. 289 - 296
Copyright
Copyright © Cambridge University Press 1988

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References

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