Banca de DEFESA: MARIA VERÔNICA DE SALES BARBOSA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : MARIA VERÔNICA DE SALES BARBOSA
DATE: 27/08/2024
TIME: 14:00
LOCAL: Departamento de Química
TITLE:

STUDY FOR THE DESIGN OF NEW OXADIAZOLES AND OXADIAZOLYL 2,3-ENOPYRANOSIDES WITH POTENT
BIOLOGICAL ACTIVITIES (ANTITUMORAL, ANTIMICROBIAL, ANTIVIRAL)

KEY WORDS:

Medicinal chemistry; 1,2,4-Oxadiazoles; Carbohydrates; Bioactivity

PAGES: 151
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUBÁREA: Química Orgânica
SPECIALTY: Síntese Orgânica
SUMMARY:

Medicinal chemistry plays an important role in the search for new classes of biologically active molecules, such as heterocyclics that show promising activities in combating/controlling various diseases. Among the heterocyclics, 1,2,4-oxadiazoles and 2,3-unsaturated O-glycosides stand out due to their broad spectrum of applications, especially in the pharmacological sector. In order to obtain new molecules with biological properties, in silico and molecular docking studies were initially carried out to determine the biological, physical, and chemical profile and also the best interaction between the proposed compounds and the selected enzymes. From these studies, the syntheses of 1,2,4-oxadiazoles derived from ethyl glycolate ester and methyl lactate were carried out, as well as the synthesis of 2,3-unsaturated O-glycosides. Initially, the syntheses of arylamide oximes were carried out and these were obtained with yields ranging from 30 to 95%, then the ethyl glycolate ester was synthesized with a yield of 50% and tri-O-acetyl-D-glycal with a yield of 70% and subsequently the 1,2,4-oxadiazoles were synthesized with yields ranging from 50 to 75%. In parallel, the 2,3-unsaturated O-glycosides were synthesized through the Ferrier rearrangement using tri-O-acetyl-D-glycal and 1,2,4-oxadiazoles as aglycone, then the 2,3-unsaturated O-glycosides were subjected to basic hydrolysis reactions, providing the hydrolyzed products with yields ranging from 40 to 56%. From the hydrolyzed compounds, an allylic oxidation was performed to produce the final compounds with yields ranging from 65 to 75%. The in silico study showed that the synthesized compounds presented good pharmacokinetic and pharmacodynamic properties. In the docking study, the binding energy ranged from -5.34 to -8.18 kcal/mol for O-glycosides and -6.62 to -8.77 kcal/mol for oxadiazoles. The compounds were subjected to antitumor and antimicrobial activity, with compounds 33e and 33f showing anticancer activity Cl50 between 6.72-24.43 μg/mL, 33d showing antibacterial activity MIC 256-512 μg/mL and 36e showing antifungal activity MIC 16-64 μg/mL. The structures of all compounds were confirmed by IR, 1H and 13C NMR spectroscopy.

 

COMMITTEE MEMBERS:
Presidente - JOAO RUFINO DE FREITAS FILHO
Interno - ***.451.424-** - JULIANO CARLO RUFINO DE FREITAS - UFCG
Interno - MARCILIO MARTINS DE MORAES
Externo ao Programa - 3022573 - JUCLEITON JOSE RUFINO DE FREITAS - UFRPEExterno à Instituição - JONH ANDERSON MACÊDO SANTOS
Externa à Instituição - LIDIANE MACEDO ALVES DE LIMA