Effects of the angiotensin II Ala-scan analogs in erythrocytic cycle of Plasmodium falciparum (in vitro) and Plasmodium gallinaceum (ex vivo)

Effects of the angiotensin II Ala-scan analogs in erythrocytic cycle of Plasmodium falciparum (in vitro) and Plasmodium gallinaceum (ex vivo)

Author Silva, Adriana Farias Google Scholar
Silva, Leandro de Souza Google Scholar
Alves, Flavio Lopes Autor UNIFESP Google Scholar
TorossianTorres, Marcelo Der Google Scholar
SaPinheiro, Ana Acacia de Google Scholar
Miranda, Antonio Google Scholar
LaraCapurro, Margareth Google Scholar
Oliveira, Vani Xavier Google Scholar
Institution Universidade Federal do ABC (UFABC)
Universidade Federal do Rio de Janeiro (UFRJ)
Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
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. (C) 2015 Elsevier Inc. All rights reserved.
Keywords Ala-scan angiotensin II
Angiotensin II
Malaria
Peptides
P. falciparum
P. gallinaceum
Language English
Sponsor Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Grant number FAPESP: 2011/10823-9
FAPESP: 2014/12938-6
FAPESP: 2011/11348-2
Date 2015-06-01
Published in Experimental Parasitology. San Diego: Academic Press Inc Elsevier Science, v. 153, p. 1-7, 2015.
ISSN 0014-4894 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 1-7
Origin http://dx.doi.org/10.1016/j.exppara.2015.02.006
Access rights Closed access
Type Article
Web of Science ID WOS:000354756000001
URI http://repositorio.unifesp.br/handle/11600/39125

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