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

•Ang II analogs interact with both P. gallinaceum and P. falciparum infected RBCs.•Native Ang II anti-plasmodial activity is preserved in Ala-scan analogs.•Some analogs are able to reduce parasite invasion in both pre and erythrocytic cycle. The anti-plasmodium activity of angiotensin II and its ana...

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Bibliographic Details
Published in:	Experimental parasitology Vol. 153; pp. 1 - 7
Main Authors:	Silva, Adriana Farias, de Souza Silva, Leandro, Alves, Flávio Lopes, Der TorossianTorres, Marcelo, de SáPinheiro, Ana Acacia, Miranda, Antonio, LaraCapurro, Margareth, Oliveira, Vani Xavier
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-06-2015
Subjects:	Ala-scan angiotensin II Angiotensin II Angiotensin II - analogs & derivatives Angiotensin II - chemical synthesis Angiotensin II - pharmacology Antimalarials - chemical synthesis Antimalarials - chemistry Antimalarials - pharmacology Erythrocytes - parasitology Humans Malaria Malaria - drug therapy Malaria - parasitology P. falciparum P. gallinaceum Peptides Peptides - chemical synthesis Peptides - chemistry Peptides - pharmacology Plasmodium falciparum Plasmodium falciparum - drug effects Plasmodium falciparum - physiology Plasmodium gallinaceum Plasmodium gallinaceum - drug effects Plasmodium gallinaceum - physiology Ala-scan angiotensin II P. gallinaceum P. falciparum Malaria Peptides Angiotensin II P.falciparum P.gallinaceum
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Summary:	•Ang II analogs interact with both P. gallinaceum and P. falciparum infected RBCs.•Native Ang II anti-plasmodial activity is preserved in Ala-scan analogs.•Some analogs are able to reduce parasite invasion in both pre and erythrocytic cycle. 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 [Ala4]-Ang II (18% of anti-plasmodium activity) that was not statistically different from control. Although [Ala8]-Ang II presented a lower biological activity (20%), it was statistically different from control. The most relevant finding was that [Ala5]-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 [Ala6]-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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0014-4894 1090-2449
DOI:	10.1016/j.exppara.2015.02.006