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

Parasitology ◽  
1990 ◽  
Vol 100 (2) ◽  
pp. 201-207 ◽  
Author(s):  
C. Ramazeilles ◽  
L. Juliano ◽  
J. R. Chagas ◽  
M. Rabinovitch
Keyword(s):  
Amino Acid ◽  
Methyl Esters ◽  
Leishmania Amazonensis ◽  
Amino Acid Esters ◽  
Cysteine Proteinases ◽  
Hydrophobic Amino Acid ◽  
Structure Activity ◽  
Reduction Assay ◽  
Mtt Reduction ◽  
Acid Esters

SUMMARYL-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.

One-pot synthesis of 4-arylidene imidazolin-5-ones by reaction of amino acid esters with isocyanates and α-bromoketones

2019 ◽  
Vol 17 (11) ◽  
pp. 3040-3047
Author(s):  
Jia-Yun Haung ◽  
Indrajeet J. Barve ◽  
Chung-Ming Sun
Keyword(s):  
Amino Acid ◽  
Multicomponent Reaction ◽  
Methyl Esters ◽  
Amino Acid Esters ◽  
One Pot ◽  
One Pot Synthesis ◽  
Acid Methyl ◽  
Acid Esters ◽  
Amino Acid Methyl Esters

A one-pot multicomponent reaction for assembling substituted 4-arylidene imidazolin-5-ones from l-amino acid methyl esters, iso-, isothio- or isoselenocyanates, and α-bromoketones has been discovered.

Die Racemisierungs-Geschwindigkeit Schiffscher Basen von Aminosäure-estern / The Racemization of the Esters of N- (p-Nitrobenzylidene) -α-amino Acids

1971 ◽  
Vol 26 (8) ◽  
pp. 762-764 ◽  
Author(s):  
I. Z. Siemion ◽  
L. Wilschowitz
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Methyl Esters ◽  
Amino Acid Esters ◽  
Butyl Esters ◽  
Acid Esters

The racemization rate of N- [p-nitrobenzylidene] -α-amino acid esters was found to be even thousand-fold smaller than that of the azlactones of N-acyl-α-amino acids. t-Butyl esters of N-[p- nitrobenzylidene]-α-amino acids are much more stable to racemization as the correspondent methyl esters.

scholarly journals Destruction of Leishmania mexicana amazonensis amastigotes within macrophages by lysosomotropic amino acid esters.

1986 ◽  
Vol 163 (3) ◽  
pp. 520-535 ◽  
Author(s):  
M Rabinovitch ◽  
V Zilberfarb ◽  
C Ramazeilles
Keyword(s):  
Amino Acid ◽  
Methyl Esters ◽  
Ph Dependence ◽  
Benzyl Ester ◽  
Mononuclear Phagocytes ◽  
Host Cells ◽  
Amino Acid Esters ◽  
High Concentrations ◽  
Secondary Lysosomes ◽  
Acid Esters

Leishmania amastigotes parasitize almost exclusively the mononuclear phagocytes of mammals. The organisms survive and multiply within acidified vacuoles (parasitophorous vacuoles; p.v.) akin to phagolysosomes. Certain amino acid esters are known to accumulate in and disrupt lysosomes. We postulated that, since Leishmania possess lysosome-like organelles, they may be susceptible to the potentially high ester concentrations attained in the p.v. We report here that L-amino acid esters can rapidly destroy intracellular Leishmania at concentrations that do not appear to damage the host cells. L-leu-OMe, which cured greater than or equal to 90% of infected macrophages at 0.8 mM concentrations, was used in most of the experiments. L-leu-OMe was only active after infection, implying inefficient transfer from secondary lysosomes to the p.v. Parasite destruction had several features in common with lysosomal and leukocyte damage induced by the esters, i.e., inactivity of D-amino acid esters, a marked pH dependence and increased killing after ester pulses at lower temperatures. Killing depended on the amino acid and on the ester substitution. The most active of the methyl esters assayed was that of leucine, followed by those of tryptophan, glutamic acid, methionine, phenylalanine, and tyrosine. Methyl esters of seven other amino acids were inactive when tested at up to 10 mM concentrations. Among leucine esters studied, benzyl ester was sixfold more active than the methyl homolog. The dipeptide L-leu-leu-OMe produced 90% cure at 0.08 mM concentrations. Leishmanicidal activity could be related to penetration of the parasites by the esters or to toxic ester hydrolysis products released in the p.v. The first hypothesis is supported by the pH-dependent destruction of isolated amastigotes by the esters. Furthermore, relatively high concentrations of L-leucine, methanol, or benzyl alcohol were not demonstrably toxic to the amastigotes. We postulate that ester concentrations sufficient to damage the intracellular amastigotes may be obtained within the p.v. after exposure of infected macrophages to the esters. Esters preferentially hydrolyzed by parasite enzymes may be expected to be leishmanicidal, but less damaging to the host.

Proteinase inhibitors protect Leishmania amazonensis amastigotes from destruction by amino acid esters

1988 ◽  
Vol 29 (2-3) ◽  
pp. 191-201 ◽  
Author(s):  
S ALFIERI ◽  
C RAMAZEILLES ◽  
V ZILBERFARB ◽  
I GALPIN ◽  
S NORMAN ◽  
...  
Keyword(s):  
Amino Acid ◽  
Proteinase Inhibitors ◽  
Leishmania Amazonensis ◽  
Amino Acid Esters ◽  
Acid Esters

The Effect of N-Substitution on the Rates of Saponification of Some Amino Acid Esters

1971 ◽  
Vol 49 (21) ◽  
pp. 3468-3476 ◽  
Author(s):  
Jocelyn E. Purdie ◽  
N. Leo Benoiton
Keyword(s):  
Amino Acid ◽  
Methyl Esters ◽  
Activation Parameters ◽  
Side Chain ◽  
Amino Acid Esters ◽  
Trans Isomers ◽  
Cis And Trans Isomers ◽  
Cis And Trans ◽  
Hydrolysis Of ◽  
Acid Esters

The saponification rates (measured at 25 ° by a titrimetric method) of the unprotonated forms of the methyl esters of glycine, alanine, leucine, valine, and phenylalanine were compared with those of the N-methyl, the N-acetyl, and the N-acetyl, N-methylamino acid analogues. N-Acetylation slightly increased or decreased the rate but N-methylation caused a reduction by as much as a factor of ten, depending on the complexity of the side-chain. The esters of the N-acetyl, N-methylamino acids, which exist as cis and trans isomers, were saponified at rates intermediate between those of the esters of the N-acetylamino acids and N-methylamino acids. Activation parameters were obtained for the phenylalanine and leucine derivatives. N-Methylation resulted in an increase in ΔH≠ and ΔS≠ which was attributed in part to solvation effects. The hydrolysis of the cationic esters of glycine and alanine was still evident at pH 11.0. N-Methylation had little effect on the rates of saponification of the charged forms.

Chiral recognition of amino-acid esters by a glucose-derived macrocyclic receptor

2021 ◽  
Author(s):  
Pit Dominique ◽  
Martin Schnurr ◽  
Bartosz Lewandowski
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Chiral Recognition ◽  
Methyl Esters ◽  
Aqueous Environment ◽  
Amino Acid Esters ◽  
Acid Methyl ◽  
Wide Range ◽  
Acid Esters ◽  
Amino Acid Methyl Esters

We report a glucose-based crown ether capable of chiral recognition of a wide range of amino-acid methyl esters in aqueous environment. The enantioselectivities towards amino-acids with extended hydrophobic side chains...

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

Parasitology ◽  
1988 ◽  
Vol 96 (2) ◽  
pp. 289-296 ◽  
Author(s):  
M. Rabinovitch ◽  
V. Zilberfarb
Keyword(s):  
Amino Acid ◽  
Methyl Ester ◽  
Methyl Esters ◽  
Hydrolytic Enzymes ◽  
Amino Acid Esters ◽  
Leishmania Mexicana ◽  
Acid Methyl ◽  
Hydrolysis Of ◽  
Acid Esters ◽  
Amino Acid Methyl Esters

SummaryL-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.

Megasomes as the targets of leucine methyl ester in Leishmania amazonensis amastigotes

Parasitology ◽  
1989 ◽  
Vol 99 (1) ◽  
pp. 1-9 ◽  
Author(s):  
J.-C. Antoine ◽  
Colette Jouanne ◽  
Antoinette Ryter
Keyword(s):  
Acid Phosphatase ◽  
Amino Acid ◽  
Methyl Ester ◽  
Proteinase Inhibitors ◽  
Morphological Changes ◽  
Leishmania Amazonensis ◽  
Biological Research ◽  
Amino Acid Esters ◽  
Parasite Viability ◽  
Acid Esters

SUMMARYCertain L-amino acid esters, such as L-leucine methyl ester (Leu-OMe), can kill intracellular and isolated Leishmania amazonensis amastigotes. Killing appears to involve ester trapping and hydrolysis within an acidified parasite compartment (M. Rabinovitch and S. C. Alfieri, 1987, Brazilian Journal of Medical and Biological Research 20, 665–74). We show here by acid phosphatase light microscopic cytochemistry and by ultrastructural morphometry that megasomes, lysosome-like amastigote organelles, are the putative parasite targets of Leu-OMe. This conclusion is supported by the following observations, (a) Control amastigotes displayed a string of electron-dense, acid phosphatase-positive megasomes mostly located in the cellular poles opposite the flagellar pockets. Incubation of the amastigotes with Leu-OMe resulted in concentration-dependent swelling and fusion of the organelles as well as decreased electron density of the internal contents. These changes, which preceded parasite disruption, were followed by the progressive loss of parasite viability and the release of acid phosphatase activity into the medium, (b) Incubation of the amastigotes with L-isoleucine methyl ester, a non-leishmanicidal compound, induced only moderate fusion of the megasomes. (c) Pre-incubation of the parasites with the proteinase inhibitors antipain and chymostatin, previously shown to confer protection from Leu-OMe toxicity, nearly completely prevented the morphological changes of megasomes. (d) Exposure of amastigotes to tryptophanamide (Trp-NH2), the leishmanicidal activity of which is not reduced by antipain and chymostatin, did not result in swelling and fusion of the megasomes. This last finding suggests that different mechanisms underlie the destruction of amastigotes by Trp-NH2 and Leu-OMe. Overall, the results are compatible with the hypothesis that Leu-OMe and other amino acid esters are trapped and hydrolysed within megasomes.

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