Banca de DEFESA: THIAGO REIXACH PIRES DE SOUZA

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : THIAGO REIXACH PIRES DE SOUZA
DATE: 08/12/2023
TIME: 09:30
LOCAL: Sala Virtual Remota https://bit.ly/Def_MSc_ThiagoSouza_PGBIOEXP
TITLE:

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KEY WORDS:

Antibiotics, Hybrid model, Phyllomedusa camba and virtual screening.

PAGES: 191
BIG AREA: Ciências Biológicas
AREA: Biologia Geral
SUMMARY:

Antibiotics, whether natural or synthetic, are the main tools in combating bacterial infections. However, the inappropriate and extensive use of antibiotics has favored the emergence of strains of bacteria that are multi-resistant to these medications, which has become a serious public health problem. One of the most prevalent species of pathogens in the hospital environment, causing infections, is the Gram-negative bacterium Acinetobacter baumannii. The World Health Organization identifies carbapenem-resistant A. baumannii as a priority in the development of new antibiotics, as these bacteria have resistance mechanisms that allow them to escape the most adverse classes of antibiotics. Therefore, in the present work, using bioinformatics and medicinal chemistry tools, we identified molecules with antimicrobial potential to be tested against A. baumannii. As strategy I, the computational construction of a hybrid molecule of antibiotics from the β-lactam and tetracycline classes, potentially effective against the penicillin-binding protein and the 30S ribosomal subunit of A. baumannii, was carried out. This hybrid molecule, called IM-TP, was used as a model for a similarity search in the PubChem database, in order to find molecules that retain the desirable characteristics of the hybrid model. The search found 295 molecular structures that retained characteristics of tetracyclines and β-lactams. As strategy II, through a partnership with Dr. Geisa Caprini Evaristo and the Center for Studies on Biomolecules Applied to Health (CEBio/FIOCRUZ-RO), they carried out in silico bioprospecting of the molecules present in the skin secretion of Phyllomedusa camba, a species of anuro, of which there are records of antimicrobial activity for its skin secretion. Using Strategy II, a total of 149 molecular structures were obtained from the PubChem database. The molecular structures found in strategies I and II were used in molecular docking against the penicillin-binding protein (PDB 3UDX) and the 30S ribosomal unit (PDB 7RYG) of A. baumannii. The molecular docking results highlighted promising molecules, both from strategy I and strategy II, with the potential to be tested in vitro against A. baumannii. For strategy I molecules, despite good of in silico results against both A. baumannii targets, no suppliers were found for these molecules, that made it impossible to perform in vitro antimicrobial activity assays against A. baumannii. Based on the in silico results of the molecules presented in the skin secretion of P. camba against the penicillin-binding protein and the 30S ribosomal subunit of A. baumannii, antimicrobial activity assays were carried out for the skin secretion of P. camba, which were discovered in MIC and IC50 data. For the skin secretion of P. camba against A. baumannii (ATCC 19606), the result was an MIC of 50 μg/mL and IC50 of 28.92 μg/mL, which seem promising when compared with information from the literature.

COMMITTEE MEMBERS:
Externa à Instituição - DEBORAH ANTUNES DOS SANTOS
Externa à Instituição - CLARICE MAIA CARVALHO - UFAC
Presidente - ***.482.422-** - NAJLA BENEVIDES MATOS - UNIR