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Antimalarial compounds derivative from angiotensin II

Grant number: 11/10823-9
Support type:Regular Research Grants
Duration: September 01, 2011 - August 31, 2013
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Vani Xavier de Oliveira Junior
Grantee:Vani Xavier de Oliveira Junior
Home Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil
Assoc. researchers:Erick Leite Bastos ; Luiz Francisco Monteiro Leite Ciscato ; Marcos Leoni Gazarini Dutra ; Margareth de Lara Capurro-Guimarães ; Wendel Andrade Alves

Abstract

Malaria affects 300 million people annually. Nevertheless, this disease has neither an effective drug treatment nor an appropriate preventive. Our research group has showed a new perspective to strive against this disease, when we related the anti-sporozoite action of angiotensin II (AII) and its inhibitory effect on the development of Plasmodium gallinaceum in Aedes aegypti. Recently, we have described the synthesis of some analogues more active than AII, which not present the pressure activity of this hormone. However, these compounds are not able to wipe out totally the parasites and rmoreover, are still susceptible to enzymatic degradation.The objective of this multidisciplinary project is obtaining an effective drug to prevent and combat the malaria. Thus, we propose the synthesis of new peptides and antimalarial prodrugs, which were designed to be employed in different evolutionary cycles of the parasite.In addition, this study aims to increase the molecular stability of these compounds against proteases, which would result in a longer action of these drugs, as well as realizing a research about the synergetic effects of drugs known in this class of bioactive peptides.The peptides will be synthesized using solid phase method, purified by RP-HPLC and characterized by different analytical techniques. In the biological assays will be verified: the molecular stability of this compound and its lytic ability "in vitro", using mature sporozoites (P. gallinaceum), collected from salivary glands of mosquito infected. Besides that, the antimalarial effects in different evolutionary steps of the parasite and its types of strains (P. falciparum and P.chabaudi) will be evaluated. (AU)

Scientific publications (11)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
SILVA, ADRIANA FARIAS; TOROSSIAN TORRES, MARCELO DER; SILVA, LEANDRO SOUZA; ALVES, FLAVIO LOPES; DE SA PINHEIRO, ANA ACACIA; MIRANDA, ANTONIO; CAPURRO, MARGARETH LARA; DE LA FUENTE-NUNEZ, CESAR; OLIVEIRA, JR., VANI XAVIER. Angiotensin II-derived constrained peptides with antiplasmodial activity and suppressed vasoconstriction. SCIENTIFIC REPORTS, v. 7, OCT 30 2017. Web of Science Citations: 4.
SILVA, ADRIANA F.; OLIVEIRA, JR., VANI X.; SILVA, LEANDRO S.; PINHEIRO, ANA A. S.; CISCATO, LUIZ F. M. L. Antiplasmodial activity of alkyl-substituted 1,2-dioxetanes against Plasmodium falciparum. Bioorganic & Medicinal Chemistry Letters, v. 26, n. 20, p. 5007-5008, OCT 15 2016. Web of Science Citations: 1.
LOPES, NICOLAS S.; YOSHITAKE, ARIANE M.; SILVA, ADRIANA F.; OLIVEIRA, JR., VANI X.; SILVA, LEANDRO S.; PINHEIRO, ANA A. S.; CISCATO, LUIZ FRANCISCO M. L. Antimalarial Effect of 3-Methoxy-1,2-Dioxetanes on the Erythrocytic Cycle of Plasmodium falciparum. CHEMICAL BIOLOGY & DRUG DESIGN, v. 86, n. 6, p. 1373-1377, DEC 2015. Web of Science Citations: 6.
SILVA, ADRIANA FARIAS; TOROSSIAN TORRES, MARCELO DER; SILVA, LEANDRO DE SOUZA; ALVES, FLAVIO LOPES; DE SA PINHEIRO, ANA ACACIA; MIRANDA, ANTONIO; CAPURRO, MARGARETH LARA; OLIVEIRA, JR., VANI XAVIER. New linear antiplasmodial peptides related to angiotensin II. Malaria Journal, v. 14, NOV 4 2015. Web of Science Citations: 3.
SILVA, ADRIANA F.; ALVES, FALVIO L.; PEDRON, CIBELE N.; TORRES, MARCELO D. T.; SILVA, LEANDRO S.; PINHEIRO, ANA A. S.; MIRANDA, ANTONIO; OLIVEIRA, JR., VANI X. Anti-plasmodial activity of bradykinin and analogs. Bioorganic & Medicinal Chemistry Letters, v. 25, n. 16, p. 3311-3313, AUG 15 2015. Web of Science Citations: 2.
SILVA, ADRIANA FARIAS; SILVA, LEANDRO DE SOUZA; ALVES, FLAVIO LOPES; TOROSSIANTORRES, MARCELO DER; DE SAPINHEIRO, ANA ACACIA; MIRANDA, ANTONIO; LARACAPURRO, MARGARETH; OLIVEIRA, JR., VANI XAVIER. Effects of the angiotensin II Ala-scan analogs in erythrocytic cycle of Plasmodium falciparum (in vitro) and Plasmodium gallinaceum (ex vivo). Experimental Parasitology, v. 153, p. 1-7, JUN 2015. Web of Science Citations: 2.
DER TOROSSIAN, TORRES MARCELO; SILVA, ADRIANA F.; ALVES, FLAVIO L.; CAPURRO, MARGARETH L.; MIRANDA, ANTONIO; XAVIER, JR., OLIVEIRA VANI. Highly Potential Antiplasmodial Restricted Peptides. CHEMICAL BIOLOGY & DRUG DESIGN, v. 85, n. 2, p. 163-171, FEB 2015. Web of Science Citations: 4.
TOROSSIAN TORRES, MARCELO DER; SILVA, ADRIANA FARIAS; SILVA, LEANDRO DE SOUZA; DE SA PINHEIRO, ANA ACACIA; JR OLIVEIRA, VANI XAVIER. Angiotensin II restricted analogs with biological activity in the erythrocytic cycle of Plasmodium falciparum. JOURNAL OF PEPTIDE SCIENCE, v. 21, n. 1, p. 24-28, JAN 2015. Web of Science Citations: 6.
RODRIGUES FERREIRA, LUIZ HENRIQUE; SILVA, ADRIANA FARIAS; TOROSSIAN TORRES, MARCELO DER; PEDRON, CIBELE NICOLASKI; CAPURRO, MARGARETH LARA; ALVES, FLAVIO LOPES; MIRANDA, ANTONIO; OLIVEIRA, JR., VANI XAVIER. Effects of Amino Acid Deletion on the Antiplasmodial Activity of Angiotensin II. INTERNATIONAL JOURNAL OF PEPTIDE RESEARCH AND THERAPEUTICS, v. 20, n. 4, p. 553-564, DEC 2014. Web of Science Citations: 2.
TORRES, MARCELO DER TOROSSIAN; SILVA, ADRIANA FARIAS; ALVES, FLAVIO LOPES; CAPURRO, MARGARETH LARA; MIRANDA, ANTONIO; OLIVEIRA JUNIOR, VANI XAVIER. The Importance of Ring Size and Position for the Antiplasmodial Activity of Angiotensin II Restricted Analogs. INTERNATIONAL JOURNAL OF PEPTIDE RESEARCH AND THERAPEUTICS, v. 20, n. 3, p. 277-287, SEP 2014. Web of Science Citations: 8.
SILVA, ADRIANA FARIAS; BASTOS, ERICK LEITE; TORRES, MARCELO DER TOROSSIAN; COSTA-DA-SILVA, ANDRE LUIS; IOSHINO, RAFAELLA SAYURI; CAPURRO, MARGARETH LARA; ALVES, FLAVIO LOPES; MIRANDA, ANTONIO; FISCHER VIEIRA, RENATA DE FREITAS; OLIVEIRA, JR., VANI XAVIER. Antiplasmodial activity study of angiotensin II via Ala scan analogs. JOURNAL OF PEPTIDE SCIENCE, v. 20, n. 8, p. 640-648, AUG 2014. Web of Science Citations: 12.

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