Banca de QUALIFICAÇÃO: ARI SOUZA GUIMARAES

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : ARI SOUZA GUIMARAES
DATE: 24/03/2022
TIME: 09:00
LOCAL: Google Meet
TITLE:

Synthesis and application of hydrazone aminoguanidines and resveratrol analogues and their hybrids with lipoic acid based on the structure of imines and amines

KEY WORDS:

Antioxidants, Aminoguanidine hydrazones, Schiff's Base, amines, antiproliferative activity, Tyrosinase, Factor
of sun protection.

 

PAGES: 110
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUMMARY:

The investigation and use of bioactive compounds with antioxidant properties has been widely
explored in recent years. Armed with the ability to modulate one or more metabolic processes,
mainly oxidative processes, the search for compounds with antioxidant properties constitutes a
area of study of paramount importance for the development of new products in the market. In this sense,
considering the importance of bioactive molecules with such properties, this work aimed to carry out a
synthetic exploration and applications of two classes of compounds. Initially, the evaluation of four
aminoguanidine hydrazone derivatives with different aromatic nuclei. Of the compounds evaluated, the
AGH-3 with the indole nucleus showed the highest antioxidant capacity with comparable results to that of
Trolox against the traditional methods of DPPH•, ABTS•+, FRAP and •NO radical sequestration. In addition, AGH-3 showed the highest antiproliferative activity against human cancer cells of
kidney (786-0) with IC50 = 6.56 µM. Additionally, in biophysical studies, the compound interacted with ctDNA
(biological target model) forming a fluorescent supramolecular complex with binding constant of
2.89×103 M-1 and acting as an intercalating ligand. Thus, these compounds show the potential of
hydrazone aminoguanidines as a strategic class of compounds for multitargeting
biological. Subsequently, the synthesis, characterization and application of compounds analogous to
resveratrol and hybrids with lipoic acid, using Schiff bases and their corresponding amines as
model structures. Thus, compounds were obtained with yields that ranged from 49 to 98% of
yields, which were characterized by 1H, 13C, Noesy and FTIR NMR. Thus, for the antioxidant assays,
the compounds showed a capacity comparable to Trolox standards, caffeic acid and ferulic acid
for the traditional methods of DPPH•, ABTS•+, FRAP radical inhibition and to Piacetannal for the method
CUPRAC (p < 0.05 for the Tukey test), however, the compounds were not active for the
Fe(II) complexation method. For the results of in vitro inhibition of the enzyme tyrosinase, the derivative
ASG21 presented the lowest IC50 of the evaluated series (0.18±0.001 mM), as well as a type of inhibition
mixed enzyme. As for the FPS-UVB results, the iminic derivatives showed a similar FPS
to the BZF-3 standard (p < 0.05 for the Tukey test), with ASG2 having the highest FPS (23.4±1.0), with this being of
in accordance with ANVISA and FDA standards. In addition, in silico ADMET studies have shown that
compounds have a low skin permeability (Kp), in addition to corroborating the studies
antioxidants, demonstrating a greater hydrophilic character of the evaluated compounds. In addition, the calculations
molecular docking theorists, demonstrated a preference of compounds for interacting with the enzyme
performed hydrophobic interactions. Finally, these results highlight the bioactive potential of the compounds
evaluated that could be explored in further studies

BANKING MEMBERS:
Interno - 2089941 - DIMAS JOSE DA PAZ LIMA
Presidente - 1820117 - ISIS MARTINS FIGUEIREDO
Externa à Instituição - LUZIA VALENTINA MODOLO - UFMG
Interna - 2120103 - MARILIA OLIVEIRA FONSECA GOULART