Banca de DEFESA: ANDRÉ RICARDO FRANÇA DA SILVA

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : ANDRÉ RICARDO FRANÇA DA SILVA
DATE: 30/01/2024
TIME: 14:00
LOCAL: Departamento de Química
TITLE:

MOLECULAR DOCKING STUDY, SYNTHESIS AND DETERMINATION OF THE ABSOLUTE CONFIGURATION BASED ON THE RETENTION FACTOR AND THE SPECIFIC ROTATION OF 2,3-UNSATURATED O-GLYCOSIDES

KEY WORDS:

Glycosides, configuration, specific rotation and retention factor

PAGES: 136
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUBÁREA: Química Orgânica
SPECIALTY: Síntese Orgânica
SUMMARY:

This work describes the synthesis, separation and determination of the absolute configuration of (R and S)-1-[3-(aryl)-1,2,4-oxadiazol-5-yl]-ethyl-2,3-dideoxy-α -D-erythro-hex-2-enopyranosides (8a-e) based on retention factor and specific rotation. The synthesis of (R and S)-1-[3-(aryl)-1,2,4-oxadiazol-5-yl]-ethyl-2,3-dideoxy-α-D-erythro-hex-2-enopyranosides was carried out from 3,4,6-tri-O-acetyl-D-glycal and different (R and S)-1-[3-aryl-1,2,4-oxadiazol-5-yl]-ethanol. This reaction provided a diastereoisomeric mixture of compounds 4a–e. Basic hydrolysis of 4a–e provided compounds 5a–h, which were carefully separated on a silica gel column yielding all diastereoisomers in pure form. The determination of the absolute configuration of compounds 5a–h was established by comparing the Rf data and specific rotation values with the standard compounds (S)-1-[3-(aryl)-1,2,4-oxadiazol-5-yl ]-ethyl-2,3-dideoxy-α-D-erythro-hex-2-enopyranosides obtained previously. by the reaction of 3,4,6-tri-O-acetyl-D-glycal with alcohols (S)-1-[3-aryl-1,2,4-oxadiazol-5-yl]-ethanol. Molecular docking simulations, carried out with 3,5-disubstituted 1,2,4-Oxadiazoles (3a-c, e), showed promising affinities with the studied targets. For E. faecalis, compounds 4a, 4b, 4c (-77.82 kcal/mol) and 4e (-81.51 kcal/mol) showed excellent ligand-receptor interaction energies, although the best ligand-receptor interaction energy was for compound 4a (-85.80 kcal/mol), followed by molecule 4b (-83.89 kcal/mol). For E. coli, compound 4c presented the best result in molecular docking (-73.77 kcal/mol), followed by compound 4e (-73.19 kcal/mol) and 4a (-73.22 kcal/mol). For S. enteritidis, the compounds that stood out the most, in relation to ligand-receptor affinity energy, were molecule 4c (-33.86 kcal/mol) followed by molecule 4e (-31.95 kcal/mol), for P aeruginosa compound 4c (-10.41 kcal/mol), 4b (-8.38 kcal/mol) and 4ª (-4.92 kcal/mol) showed the best results in molecular docking. The biological activities tested for compounds 4a, 4b, 4c and 4e presented MIC equal to 1.75 µg/mL for Enterococcus faecalis, for Escherichia coli compounds 4b and 4c presented the lowest MIC of 1.75 µg/mL. Compounds 4b, 4a and 4c showed MIC of 0.875 µg/mL for Pseudomonas aeruginosa. Compounds 4e and 4c presented the lowest MIC for Salmonella enteritidis, with a MIC of 3.5 µg/mL.

COMMITTEE MEMBERS:
Presidente - JOAO RUFINO DE FREITAS FILHO
Externo ao Programa - ***.337.024-** - ALEX FRANCE MESSIAS MONTEIRO - UFPB
Externo ao Programa - ***.571.514-** - JONH ANDERSON MACÊDO SANTOS - IFPE
Externo ao Programa - 3022573 - JUCLEITON JOSE RUFINO DE FREITAS - UFRPE