title: Effects of the angiotensin II Ala-scan analogs in erythrocytic cycle of Plasmodium falciparum (in vitro) and Plasmodium gallinaceum (ex vivo).
abstract: The anti-plasmodium activity of angiotensin II and its analogs have been described in different plasmodium species. Here we synthesized angiotensin II Ala-scan analogs to verify peptide-parasite invasion preservation with residue replacements. The analogs were synthesized by 9-fluorenylmethoxycarbonyl (Fmoc) and tert-butyloxycarbonyl (t-Boc) solid phase methods, purified by liquid chromatography and characterized by mass spectrometry. The results obtained in Plasmodium falciparum assays indicated that all analogs presented some influence in parasite invasion, except [Ala(4)]-Ang II (18% of anti-plasmodium activity) that was not statistically different from control. Although [Ala(8)]-Ang II presented a lower biological activity (20%), it was statistically different from control. The most relevant finding was that [Ala(5)]-Ang II preserved activity (45%) relative to Ang II (47%). In the results of Plasmodium gallinaceum assays all analogs were not statistically different from control, except [Ala(6)]-Ang II, which was able to reduce the parasitemia about 49%. This approach provides insight for understanding the importance of each amino acid on the native Ang II sequence and provides a new direction for the design of potential chemotherapeutic agents without pressor activity.
authors.affiliation: Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, SP, Brazil.
authors.forename: Adriana Farias
authors.initials: AF
authors.lastname: Silva
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Leandro
authors.initials: L
authors.lastname: de Souza Silva
authors.affiliation: Departamento de Biofísica, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: Flávio Lopes
authors.initials: FL
authors.lastname: Alves
authors.affiliation: Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, SP, Brazil.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Der TorossianTorres
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Ana Acacia
authors.initials: AA
authors.lastname: de SáPinheiro
authors.affiliation: Departamento de Biofísica, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: Antonio
authors.initials: A
authors.lastname: Miranda
authors.affiliation: Departamento de Parasitologia, Instituto de Ciências Biomédicas II, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Margareth
authors.initials: M
authors.lastname: LaraCapurro
authors.affiliation: Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, SP, Brazil. Electronic address: vani.junior@ufabc.edu.br.
authors.forename: Vani Xavier
authors.initials: VX
authors.lastname: Oliveira
mesh_terms: D000804:Angiotensin II / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004912:Erythrocytes / Q000469:parasitology*; D006801:Humans; D008288:Malaria / Q000188:drug therapy / Q000469:parasitology*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000502:physiology; D010964:Plasmodium gallinaceum / Q000187:drug effects* / Q000502:physiology
chemical_list: D000962:Antimalarials; D010455:Peptides; D000804:Angiotensin II
keywords: Ala-scan angiotensin II; Angiotensin II; Malaria; P.falciparum; P.gallinaceum; Peptides