Banca de DEFESA: PALOMA KAROLINE DA SILVA BRASIL
Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : PALOMA KAROLINE DA SILVA BRASIL
DATE: 09/03/2023
TIME: 14:00
LOCAL: SESSÃO DE VIDEOCONFERÊNCIA (LINK A DEFINIR)
TITLE:
Teixobactin: design of new analogues by scaffold hopping
KEY WORDS:
Teixobactin; Scaffold Hopping, Pharmacophore-driven; bacterial resistance
PAGES: 69
BIG AREA: Ciências da Saúde
AREA: Farmácia
SUMMARY:
Bacterial resistance is one of the most discussed issues in recent years, due to the irrational use of
antimicrobials, making “superbugs” one of the main issues discussed in several countries.
Teixobactin was discovered in 2015 by a group of researchers from NovaBiotic Pharmaceuticals,
which showed antimicrobial activity making it a promising substance with potential for clinical
use, however, it presents challenges in its synthesis, where several prototypes have already been
proposed with the intuitive to enable its commercial use. In this scenario, virtual tools are widely
used by the pharmaceutical industry in drug discovery and, in the present work, tools such as
molecular dynamics, scaffold hopping and molecular docking were used to obtain a specific with
effective interaction with Lipid II. Thus, the objective of this study was to build and study the
mode of interaction of Teixobactin and use this information to protect the simplest sense.
Replacement of the central chemical structure by another molecular pattern was advocated. We
performed a search for data and studies which addressed the most important chemical groups for
the Teixobactin molecule and performed molecular docking to obtain the best interaction
complexes between the ligand and the target receptor. From the best complexes, we performed a
Molecular Dynamics simulation in order to obtain the highest number of reproductions. From
this, we define the most representative structural skeleton for the biological activity and carry out
tolerable functional group substitutions for the molecule. A new molecular docking was
performed to identify receptor complexes with relevant in the target receptor. We obtained 17
typical ones, which we felt had a good interaction with lipid II compared to the original
Teixobactin molecule.
COMMITTEE MEMBERS:
Presidente - 1893445 - EUZEBIO GUIMARAES BARBOSA
Interno - 2275890 - MARCELO DE SOUSA DA SILVA
Externo à Instituição - RICARDO OLIMPIO DE MOURA - UEPB