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New linear antiplasmodial peptides related to angiotensin II.

Silva AF, Torres MD, Silva Lde S, Alves FL, Pinheiro AA, Miranda A, Capurro ML, Oliveira VX - Malar. J. (2015)

Bottom Line: The results indicate two short-peptides constituted by hydrophobic residues (5 and 6) with antiplasmodial activity in these models, 89 and 94 % of biological activity against P. gallinaceum sporozoite, respectively, and around 50 % of activity against P. falciparum.This class of peptides can be explored, as anti-malarial drugs, after in vivo model tests.Graphical abstract: The most active peptide presented 94 % activity on P. gallinaceum sporozoites and 53 % inhibited P. falciparum ring forms invasion.

View Article: PubMed Central - PubMed

Affiliation: Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Rua Santa Adélia, 166, Santo André, SP, 09210-170, Brazil. adrianafarias.silva@gmail.com.

ABSTRACT

Background: Antiplasmodial activities of angiotensin II and its analogues have been extensively investigated in Plasmodium gallinaceum and Plasmodium falciparum parasite species. Due to its vasoconstrictor property angiotensin II cannot be used as an anti-malarial drug.

Methods: This work presents the solid-phase syntheses and liquid chromatography and mass spectrometry characterization of ten linear peptides related to angiotensin II against mature P. gallinaceum sporozoites and erythrocyte invasion by P. falciparum. Conformational analyses were performed by circular dichroism. IC50 assays were performed to identify the ideal concentration used on the biological tests and haemolytical erythrocytic assays were made to verify the viability of the biological experiments. The contractile responses of the analogues were made to evaluate if they are promising candidates to be applied as antiplasmodial drugs.

Results: The results indicate two short-peptides constituted by hydrophobic residues (5 and 6) with antiplasmodial activity in these models, 89 and 94 % of biological activity against P. gallinaceum sporozoite, respectively, and around 50 % of activity against P. falciparum. Circular dichroism spectra suggested that all the peptides adopted β-turn conformation in different solutions, except peptide 3. Besides the biological assays IC50, the haemolysis assays and contractile response activities were applied for peptides 5 and 6, which did not present expressive results.

Conclusions: The hydrophobic portion and the arginine, tyrosine, proline, and phenylalanine, when present on peptide primary sequence, tend to increase the antiplasmodial activity. This class of peptides can be explored, as anti-malarial drugs, after in vivo model tests. Graphical abstract: The most active peptide presented 94 % activity on P. gallinaceum sporozoites and 53 % inhibited P. falciparum ring forms invasion.

No MeSH data available.


Related in: MedlinePlus

IC50 value for each assay. Peptides 5 and 6 were diluted in seven concentrations [(10−4; 10−6; 10−8; 10−9; 10−10; 10−12; 10−14) mol L−1] giving 7–65 % inhibition. Data have been normalized due difference between control of each assay. The IC50 data were analysed by GraphPad Prism analysis. Parameters: non-linear regression; log (inhibitor) vs response equation was chosen and least square (ordinary) fit method was applied (mean ± standard deviation, n = 2)
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Fig4: IC50 value for each assay. Peptides 5 and 6 were diluted in seven concentrations [(10−4; 10−6; 10−8; 10−9; 10−10; 10−12; 10−14) mol L−1] giving 7–65 % inhibition. Data have been normalized due difference between control of each assay. The IC50 data were analysed by GraphPad Prism analysis. Parameters: non-linear regression; log (inhibitor) vs response equation was chosen and least square (ordinary) fit method was applied (mean ± standard deviation, n = 2)

Mentions: The IC50 value represents the peptide concentration producing a 50 % reduction in the number of P. falciparum rings formed compared to peptide-free control cultures. The concentration of each peptide required to inhibit the rings form by 50 % (IC50) was determined by testing seven concentrations giving 7–65 % inhibition and then interpolating IC50 by non-linear regression analysis as previously cited. Data are shown in Fig. 4.Fig. 4


New linear antiplasmodial peptides related to angiotensin II.

Silva AF, Torres MD, Silva Lde S, Alves FL, Pinheiro AA, Miranda A, Capurro ML, Oliveira VX - Malar. J. (2015)

IC50 value for each assay. Peptides 5 and 6 were diluted in seven concentrations [(10−4; 10−6; 10−8; 10−9; 10−10; 10−12; 10−14) mol L−1] giving 7–65 % inhibition. Data have been normalized due difference between control of each assay. The IC50 data were analysed by GraphPad Prism analysis. Parameters: non-linear regression; log (inhibitor) vs response equation was chosen and least square (ordinary) fit method was applied (mean ± standard deviation, n = 2)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4634797&req=5

Fig4: IC50 value for each assay. Peptides 5 and 6 were diluted in seven concentrations [(10−4; 10−6; 10−8; 10−9; 10−10; 10−12; 10−14) mol L−1] giving 7–65 % inhibition. Data have been normalized due difference between control of each assay. The IC50 data were analysed by GraphPad Prism analysis. Parameters: non-linear regression; log (inhibitor) vs response equation was chosen and least square (ordinary) fit method was applied (mean ± standard deviation, n = 2)
Mentions: The IC50 value represents the peptide concentration producing a 50 % reduction in the number of P. falciparum rings formed compared to peptide-free control cultures. The concentration of each peptide required to inhibit the rings form by 50 % (IC50) was determined by testing seven concentrations giving 7–65 % inhibition and then interpolating IC50 by non-linear regression analysis as previously cited. Data are shown in Fig. 4.Fig. 4

Bottom Line: The results indicate two short-peptides constituted by hydrophobic residues (5 and 6) with antiplasmodial activity in these models, 89 and 94 % of biological activity against P. gallinaceum sporozoite, respectively, and around 50 % of activity against P. falciparum.This class of peptides can be explored, as anti-malarial drugs, after in vivo model tests.Graphical abstract: The most active peptide presented 94 % activity on P. gallinaceum sporozoites and 53 % inhibited P. falciparum ring forms invasion.

View Article: PubMed Central - PubMed

Affiliation: Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Rua Santa Adélia, 166, Santo André, SP, 09210-170, Brazil. adrianafarias.silva@gmail.com.

ABSTRACT

Background: Antiplasmodial activities of angiotensin II and its analogues have been extensively investigated in Plasmodium gallinaceum and Plasmodium falciparum parasite species. Due to its vasoconstrictor property angiotensin II cannot be used as an anti-malarial drug.

Methods: This work presents the solid-phase syntheses and liquid chromatography and mass spectrometry characterization of ten linear peptides related to angiotensin II against mature P. gallinaceum sporozoites and erythrocyte invasion by P. falciparum. Conformational analyses were performed by circular dichroism. IC50 assays were performed to identify the ideal concentration used on the biological tests and haemolytical erythrocytic assays were made to verify the viability of the biological experiments. The contractile responses of the analogues were made to evaluate if they are promising candidates to be applied as antiplasmodial drugs.

Results: The results indicate two short-peptides constituted by hydrophobic residues (5 and 6) with antiplasmodial activity in these models, 89 and 94 % of biological activity against P. gallinaceum sporozoite, respectively, and around 50 % of activity against P. falciparum. Circular dichroism spectra suggested that all the peptides adopted β-turn conformation in different solutions, except peptide 3. Besides the biological assays IC50, the haemolysis assays and contractile response activities were applied for peptides 5 and 6, which did not present expressive results.

Conclusions: The hydrophobic portion and the arginine, tyrosine, proline, and phenylalanine, when present on peptide primary sequence, tend to increase the antiplasmodial activity. This class of peptides can be explored, as anti-malarial drugs, after in vivo model tests. Graphical abstract: The most active peptide presented 94 % activity on P. gallinaceum sporozoites and 53 % inhibited P. falciparum ring forms invasion.

No MeSH data available.


Related in: MedlinePlus