New linear antiplasmodial peptides related to angiotensin II

• Published in: Malaria journal Vol. 14; no. 1; p. 433
• Main Authors: Silva, Adriana Farias, Torres, Marcelo Der Torossian, Silva, Leandro de Souza, Alves, Flávio Lopes, Pinheiro, Ana Acácia de Sá, Miranda, Antonio, Capurro, Margareth Lara, Oliveira, Jr, Vani Xavier
• Format: Journal Article
• Language: English
• Published: England BioMed Central 04-11-2015
• Subjects: Aedes - parasitology; Angiotensin II - adverse effects; Angiotensin II - analogs & derivatives; Angiotensin II - pharmacology; Animals; Antimalarials - adverse effects; Antimalarials - chemical synthesis; Antimalarials - pharmacology; Biological Products - chemical synthesis; Biological Products - pharmacology; Chickens - parasitology; Chromatography, Liquid; Erythrocytes - parasitology; Hemolysis; Inhibitory Concentration 50; Malaria; Mass Spectrometry; Mice, Inbred C57BL; Microbial Sensitivity Tests; Muscle Contraction - drug effects; Peptides - chemical synthesis; Peptides - pharmacology; Plasmodium falciparum - drug effects; Plasmodium gallinaceum - drug effects; Stomach - drug effects
• ISSN: 1475-2875; 1475-2875
• DOI: 10.1186/s12936-015-0974-y

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.
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.
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.
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.