Banca de QUALIFICAÇÃO: LANA PATRICIA DE OLIVEIRA BARROS PINTO DE OLIVEIRA

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : LANA PATRICIA DE OLIVEIRA BARROS PINTO DE OLIVEIRA
DATE: 27/02/2025
TIME: 15:00
LOCAL: Centro de Estudos e pesquisas da Amazônia – CEPA/UNIFAP
TITLE:

Design of Bioactive Compounds Based on Ligand-Structure with Potential Antibacterial Activity in Strains of MRSA and VRSA.

KEY WORDS:

bacterial resistance; virtual antibacterial screening; MRSA, VRSA, rational antibiotic planning.

PAGES: 76
BIG AREA: Ciências Biológicas
AREA: Biofísica
SUBÁREA: Biofísica Molecular
SUMMARY:

Staphylococcus aureus is a highly prevalent microorganism with high mortality rates. The
MRSA and VRSA strains of S. aureus, studied in this project, show resistance mechanisms to
the main antibiotics on the market, driving the need for the development of new bioactive
compounds. Computer Aided Bioactive Compound Design is a set of tools that allow
understanding, predicting, or explaining the behavior of molecules in biological systems. With
technological advances, such computational methods have gained more and more space in the
Planning and Development of Drugs, in view of their predictive role, accelerating the
identification of bioactive compounds. This work aims to identify new entities with
antibacterial activity against MRSA and VRSA strains, from polyoxygenated dibenzofuran
derivatives, through Virtual Screening based on Ligands (Pharmacophore) and Structure,
predictions of Biological Activity, predictions of Lipophilicity and Water solubility, as well as
in vitro Biological and Antioxidant activity assays. For this work, molecules were selected in
ascending order of minimum inhibitory concentration (MIC) values for ATCC25923 S. aureus,
ranging from 0.24 μg/mL to >30 μg/mL from the study by Oramas-Royo et al., (2017). The
geometric optimization of the 3D structure of the molecules was performed in the ChemSketch
software using the MM+ method. The pharmacophoric model was obtained from the
Pharmagist server, with a 3D structure from the aligned pharmacophoric characteristics,
obtaining a score equal to 32.476. For the Virtual Screening based on Pharmacophore, the
Pharmit platform was used, where the search for molecules was carried out in the MolPort
database (Top100). The similarity between the molecules was analyzed by the Tanimoto
Similarity Index, calculated in the BindingDB webserver. Predictions of toxicological and
pharmacokinetic properties (ADME/Tox) were performed on ProTox II and PREADMET
webservers. The molecules that presented satisfactory results in the pharmacokinetic and
toxicological analyzes were submitted to Biological Activity prediction, using the PASS online
server. Antibacterial activity was predicted via Antibac-Pred, which revealed that the pivot
molecules, oxacillin, methicillin, and the molecule MolPort-001-741-320 (LB320) showed
activity against S. aureus. The Molecular Docking study was carried out through the DockThor
online server. The molecular targets of the MRSA and VRSA strains were obtained from the
Protein Data Bank database, with the respective PDB ID's codes: 4CJN and 4GSY. The
promising molecule LB320 presented the best results in the Docking simulations. The
lipophilicity and water solubility values were predicted in the SwissADME online server, where
the commercial compounds and the LB255 molecule presented hydrophilic character, however,
the LB320 and LB415 molecules were more lipophilic, however having water solubility. For
the in vitro biological assay, standard bacterial cultures of Methicillin-resistant Staphylococcus
aureus ATCC700699 (MRSA) and Vancomycin resistant Staphylococcus aureus NRS402
(VRSA) will be used. The Minimum Inhibitory Concentration (MIC) will be determined by the
microplate dilution technique (96 wells) according to CLSI standard M7-A6. The in silico
prediction of the antioxidant activity of the structures will be performed using the PASS online
server and in vitro using the DPPH and ABTS methodologies.

COMMITTEE MEMBERS:
Externo ao Programa - 1761020 - ALDO APARECIDO PROIETTI JUNIOR - nullPresidente - ***.859.385-** - GABRIEL ARAÚJO DA SILVA - UFRN
Externo à Instituição - VICTOR HUGO GOMES SALES - IFAP