title: A study of the anti-plasmodium activity of angiotensin II analogs.
abstract: Controlling the dissemination of malaria requires the development of new drugs against its etiological agent, a protozoan of the Plasmodium genus. Angiotensin II and its analog peptides exhibit activity against the development of immature and mature sporozoites of Plasmodium gallinaceum. In this study, we report the synthesis and characterization of angiotensin II linear and cyclic analogs with anti-plasmodium activity. The peptides were synthesized by a conventional solid-phase method on Merrifield's resin using the t-Boc strategy, purified by RP-HPLC and characterized by liquid chromatography/ESI (+) MS (LC-ESI(+)/MS), amino acid analysis, and capillary electrophoresis. Anti-plasmodium activity was measured in vitro by fluorescence microscopy using propidium iodine uptake as an indicator of cellular damage. The activities of the linear and cyclic peptides are not significantly different (p < 0.05). Kinetics studies indicate that the effects of these peptides on plasmodium viability overtime exhibit a sigmoidal profile and that the system stabilizes after a period of 1 h for all peptides examined. The results were rationalized by partial least-square analysis, assessing the position-wise contribution of each amino acid. The highest contribution of polar amino acids and a Lys residue proximal to the C-terminus, as well as that of hydrophobic amino acids in the N-terminus, suggests that the mechanism underlying the anti-malarial activity of these peptides is attributed to its amphiphilic character.
authors.affiliation: Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, SP, Brazil.
authors.forename: Mayra
authors.initials: M
authors.lastname: Chamlian
authors.forename: Erick L
authors.initials: EL
authors.lastname: Bastos
authors.forename: Ceres
authors.initials: C
authors.lastname: Maciel
authors.forename: Margareth L
authors.initials: ML
authors.lastname: Capurro
authors.forename: Antonio
authors.initials: A
authors.lastname: Miranda
authors.forename: Adriana F
authors.initials: AF
authors.lastname: Silva
authors.forename: Marcelo Der T
authors.initials: MD
authors.lastname: Torres
authors.forename: Vani X
authors.initials: VX
authors.lastname: Oliveira
mesh_terms: D000595:Amino Acid Sequence; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002645:Chickens; D004353:Drug Evaluation, Preclinical; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D010964:Plasmodium gallinaceum / Q000187:drug effects*; D034101:Sporozoites / Q000187:drug effects
chemical_list: D000962:Antimalarials; D000804:Angiotensin II
keywords: Plasmodium gallinaceum; angiotensin II; lactam bridge; malaria; peptides; sporozoites