Banca de QUALIFICAÇÃO: DAIANA DE FATIMA PORTELLA FRANCO

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
DISCENTE : DAIANA DE FATIMA PORTELLA FRANCO
DATA : 19/12/2018
HORA: 10:00
LOCAL: Instituto de Química
TÍTULO:

 

Synthesis and biological evaluation of Aril Sufonil Amino Pyrazoles designed as Hybrid Inhibitors of the enzymes NS2 / NS3 and NS5 for the treatment of dengue.

PALAVRAS-CHAVES:

dengue, NS3 / NS2 protease, NS5B polymerase, Susuki, Sonogashira.

PÁGINAS: 20
GRANDE ÁREA: Ciências Exatas e da Terra
ÁREA: Química
RESUMO:

Dengue fever is a viral infection mainly transmitted by the Aedes aegypti mosquito, with about 390 million infections occurring annually worldwide. Dengue virus (DENV) belongs to the Flaviviridae family and comprises four distinct serotypes (DENV1-4). The severity of infections may be asymptomatic or progress to more severe conditions such as dengue hemorrhagic fever and dengue shock syndrome. The individual, after recovery, acquires immunity against the serotype for which he was infected, but a subsequent infection with a different serotype is more likely to result in severe disease. To date, there is no effective drug against DENV. The DENV genome encodes only ten proteins, including non-structural proteins such as NS2B / NS3 protease and NS5B polymerase, which are critical to the reproductive cycle of the virus. Both DENV proteins are attractive targets for the discovery of antiviral compounds for the treatment of dengue. Thus, this project is premised on the planning of hybrid aryl sulfonyl amino pyrazoles compounds designed as inhibitors of NS2B / NS3 protease and NS5B polymerase enzymes from pyrazole esters described in the literature as potent inhibitors of the DENV NS2 / NS3 protease enzyme; and sulfonyl amide derivatives identified as inhibitors of NS5B polymerase. The hybrid series will make use of the coupling reactions of Suzuki and Sonogashira in the presence of palladium complexes acting as catalysts. The bioactivity profile of the synthesized compounds will be performed in in vitro models of inhibition of the NS3 / NS2 protease and the NS5B polymerase enzyme. The interactions between the series of compounds and the enzymes, NS3 / NS2 protease and NS5B polymerase will be investigated by theoretical molecular modeling methods, using their respective crystallographic structures PDB 3U1L and PDB 5HMZ, using GOLD (CCDC) and PC Spartan Pro (Wavefunction).

MEMBROS DA BANCA:
Externo à Instituição - DANIEL PAIS PIRES VIEIRA - IFRJ
Presidente - 1177598 - ROSANE NORA CASTRO
Externo à Instituição - VAGNER DANTAS PINHO