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The anti-leishmanial activity of dipeptide esters on Leishmania amazonensis amastigotes

Published online by Cambridge University Press:  06 April 2009

C. Ramazeilles ,
L. Juliano ,
J. R. Chagas  and
M. Rabinovitch
C. Ramazeilles
Affiliation:
Unité d'Immunoparasitologie, Institut Pasteur, and Centre National de Ia Recherche Scientifique (A040361), 25 rue du Docteur Roux, 75724 Paris, France
L. Juliano
Affiliation:
Department de Biofisica, Escola Paulista de Medicina, Rua 3 de Maio 100, 04044 São Paulo SP, Brazil
J. R. Chagas
Affiliation:
Department de Biofisica, Escola Paulista de Medicina, Rua 3 de Maio 100, 04044 São Paulo SP, Brazil
M. Rabinovitch
Affiliation:
Unité d'Immunoparasitologie, Institut Pasteur, and Centre National de Ia Recherche Scientifique (A040361), 25 rue du Docteur Roux, 75724 Paris, France
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Summary

L-Amino acid esters, such as L-Leu-OMe, kill Leishmania amazonensis amastigotes by a mechanism which appears to involve ester hydrolysis by cysteine proteinases located in the parasite megasomes. We have examined the killing of isolated amastigotes by L-dipeptide esters and derived some structure-activity correlations. Toxicity of the compounds for the parasites was measured by a tetrazolium (MTT) reduction assay. The results show that active dipeptide esters contained at least I hydrophobic amino acid (Leu, Ile, Val, Phe or Trp). The activity of homodipeptide methyl esters depended on the nature of the amino acid, as indicated by the following series: Phe-Phe-OMe < Val-Val-OMe < Leu-Leu-OMe < Trp-Trp-OMe < Ile-Ile-OMe. The nature of the amino acids in Leu-X-OMe and X-Leu-OMe was relatively unimportant when X was Phe, Trp or Val. However, when X was Ala or Gly, Leu-X-OMe was several-fold more active than X-Leu-OMe.

Keywords

Leishmania amazonensisamastigotesdipeptide esters
Type
Research Article
Information
Parasitology , Volume 100 , Issue 2 , April 1990 , pp. 201 - 207
Copyright
Copyright © Cambridge University Press 1990

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