Banca de QUALIFICAÇÃO: JOSÉ RONIELE DO NASCIMENTO MONTEIRO

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : JOSÉ RONIELE DO NASCIMENTO MONTEIRO
DATE: 29/09/2023
TIME: 09:00
LOCAL: Sala Virtual Remora - Teams https://bit.ly/QualifDoc_JoseRoniele_PGBioExp
TITLE:

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KEY WORDS:

Antiparasitic peptides. Ocelatins. Leptodactylus. P. falciparum. Leishmania sp.

PAGES: 82
BIG AREA: Ciências Biológicas
AREA: Biologia Geral
SUMMARY:

Malaria and leishmaniasis are diseases that afflict millions of people annually in Brazil and around the world. The therapy commonly used in the treatment of these diseases is based on the use of drugs that cause severe side effects under an extensive treatment regimen, resulting in low adherence and a high rate of treatment abandonment. There is a continuous need to search for new therapies against these parasitic diseases that are effective, safe, and easy to administer. In order to expand the options for the development of new antiparasitic drugs, antimicrobial peptides (AMPs) emerge as promising agents for the development of new therapies against pathogens resistant to conventional antibiotics, possessing potent activity against a variety of microorganisms using different mechanisms to eliminate invasive pathogens. With the aim of evaluating the biological activity of AMPs, two synthetic peptides, OKN and OKDAB, were designed based on the antimicrobial peptide ocelatina K-1 extracted from the frog Leptodactylus knudseni. The peptides were designed with the help of online tools and exhibited different charges and amphipathicity. These peptides were investigated against Plasmodium falciparum W2 and L. amazonensis, where their halfmaximal inhibitory concentration (IC50) was determined. Cytotoxic concentrations (CC50) of all peptides against HepG2 and J774 cells were determined, and a hemolysis test was performed. Studies of interaction between OK1 and membranes were carried out using giant unilamellar vesicles (GUVs) with different phospholipid compositions, including POPC:POPG (9:1), POPC:POPG (8:2), POPC:POPG (1:1), and POPC:Chol (9:1). The peptides exhibited distinct charges of 3.1, 5.1, and 7.1 for OK1, OKN, and OKDAB, respectively. The results show that charge is one of the important chemical parameters for the action of peptides, considering that OKDAB, with the highest charge, showed the best results against P. falciparum (IC50 0.73 µM) and L. amazonensis (IC50 47.33 µM), although it was considered inactive against L. amazonensis. However, it was also observed that the high charge not only potentiated the activity of the peptides but also exhibited cytotoxicity against the host cell, with CC50 values of 56.49, 231.11, and 8.6 µM for OK1, OKN, and OKDAB, respectively. Promising results were obtained in assays against P. falciparum, with IC50 values of ≥100, 3.67, and 0.73 µM for OK1, OKN, and OKDAB, respectively. It is noteworthy that peptides with a higher charge showed better antiplasmodial activity; however, the one with the highest charge of 7.1 (OKDAB) exhibited hemolytic activity, whereas OK1 and OKN with lower charges did not display this characteristic. GUV assays revealed that the mechanism of action of OK1 involves the formation of stable pores in anionic membranes, with cholesterol acting as an inhibitor of its activity. The results indicate that charge is a fundamental parameter for the action of AMPs derived from ocelatina K-1 and that the peptides hold promising prospects for exploration and application in studies against malaria and leishmaniasis parasites.

COMMITTEE MEMBERS:
Externo à Instituição - OCTAVIO LUIZ FRANCO - UCDB
Externo à Instituição - CÉSAR JÚLIO MOREIRA DE BRITO
Presidente - ***.429.088-** - CAROLINA BIONI GARCIA TELES - FIOCRUZ