Banca de QUALIFICAÇÃO: ALLANNY ALVES FURTADO

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : ALLANNY ALVES FURTADO
DATE: 21/12/2020
TIME: 08:00
LOCAL: Videoconferência
TITLE:

STRUCTURAL CHARACTERIZATION AND EVALUATION OF ANTIBACTERIAL ACTIVITY in vitro AND in vivo OF STIGMURIN ANALOGUES PEPTIDES

KEY WORDS:

Tityus stigmurus, Scorpion, Antimicrobial Peptides, Multifunctional Peptides, Cationic Peptides.

PAGES: 126
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

Antimicrobial resistance is considered a public health problem because it affects not only the hospital environment but also the communities, hindering the success of therapy and increasing costs in public and private hospitals. In addition, the speed with which microorganisms acquire resistance is greater than the production of new antimicrobials, leading to the need to search for molecules in different natural sources with an antibiotic effect. In this context, the scorpion venom consists of a rich source of biomolecules with high antimicrobial potential. Stigmurin, a peptide present in the venom of the scorpion Tityus stigmurus, showed antibacterial activity against Gram-positive bacteria and yeasts of the genus Candida, with antiproliferative effect against different cancer cells and low toxicity in human erythrocytes in vitro. In order to expand the antimicrobial potential of the native peptide, analogues peptides were designed in silico, with point substitutions of amino acids in the primary sequence for lysine. The structural characterization of the analogues peptides, called StigA8 and StigA18, were obtained by structural prediction, molecular modeling and circular dichroism, with biocompatibility being evaluated in human red blood cells, murine fibroblasts and Galleria mellonella moth larvae. The antibacterial activity against Gram-positive and negative strains and the antibiofilm action of the peptides were evaluated in vitro, as well as the antibacterial effect in vivo on larvae infected with Staphylococcus aureus. Considering the multifunctionality of antimicrobial peptides, the antiparasitic action of StigA8 and StigA18 on the epimastigotes and trypomastigotes forms of Trypanossoma cruzi and the antiproliferative effect in cancer cell lines were evaluated in vitro. The analogues peptides presented a conformation mostly in α-helix, mainly in environments that mimic biological membranes, as well as, higher cationicity and hydrophobic moment indexes in relation to the prototype molecule. StigA8 and StigA18 revealed low hemolytic activity, with a 50% murine fibroblast cytotoxicity index at a concentration of 20 µM and 12.3 µM, respectively, and no toxicity on the larvae. Both analogues peptides showed antimicrobial activity for gram-positive strains, with antibiofilm action against S. aureus in low concentrations, causing damage such as matrix destruction, cell membrane invaginations, roughness and reduced cell diameter. StigA8 and StigA18 showed antibacterial effect in vivo, increasing larval survival by 75% and 60%, respectively, at the peak of infection. The analogues peptides also showed high trypanocidal activity on T. cruzi and antiproliferative potential at low concentrations. Therefore, StigA8 and StigA18 are promising molecules for the development of new anti-infective and anticancer drugs.

BANKING MEMBERS:
Externa à Instituição - ANA CAROLINA DE OLIVEIRA NEVES MENEZES
Presidente - 1880243 - DANIEL CARLOS FERREIRA LANZA
Interno - 2213126 - VALTER FERREIRA DE ANDRADE NETO