Banca de QUALIFICAÇÃO: NATHALIA FONSECA NADUR

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : NATHALIA FONSECA NADUR
DATE: 05/05/2025
TIME: 10:00
LOCAL: Remoto
TITLE:

SYNTHESIS AND BIOLOGICAL EVALUATION OF STRUCTURALLY OPTIMIZED FLAVONOIDS AS ALLOSTERIC MODULATORS OF ZIKA VIRUS NS2B/NS3 PROTEASE

KEY WORDS:

Zika virus (ZIKV), NS2B/NS3 protease, allosteric inhibitors, synthetic flavonoids, sulfonamides, amides

PAGES: 16
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUBÁREA: Química Orgânica
SPECIALTY: Síntese Orgânica
SUMMARY:

Zika is a viral infection transmitted mainly by the Aedes aegypti mosquito, with 22,885 cases reported in the Americas in 2020, of which 83% occurred in Brazil. The Zika virus (ZIKV) has a variable clinical spectrum, from asymptomatic infections to severe neurological complications. Vertical transmission (mother-fetus) is one of its most critical characteristics and can cause congenital malformations, such as microcephaly. The ZIKV genome encodes ten proteins, including the NS2B/NS3 protease, a priority target for developing antivirals. This enzyme, essential for viral replication and persistence, processes the viral polyprotein into functional components and has been widely studied for its therapeutic potential. However, the protease's active site exhibits a preference for cationic and hydrophilic ligands, properties associated with low membrane permeability. Thus, this work aims to identify allosteric inhibitors of NS2B/NS3pro to block ZIKV replication by synthesizing flavonoids strategically functionalized with sulfonamide or amide groups. The syntheses of series A and B follow an initial convergent pathway involving the Claisen-Schmidt condensation to form chalcones and subsequent oxidative cyclization to construct the flavonic nucleus. The strategic divergence occurs in the conclusive steps: targeted sulfonation (A) and selective alkylation (B), conferring distinct functionalizations. Enzymatic inhibition and kinetic assays of the NS2B/NS3 protease will be conducted, in addition to evaluating the antiviral activity of the compounds against ZIKV. Cytotoxicity and cell permeability will be investigated to determine the safety profile and bioavailability. In parallel, theoretical methods (molecular modeling) will be used to elucidate the interaction profile of the compounds with the allosteric regions of the protease, integrating experimental and computational data

COMMITTEE MEMBERS:
Interno - 2624418 - CLAUDIO EDUARDO RODRIGUES DOS SANTOS
Interno - 3292567 - EDUARDO HILLMANN WANDERLIND
Externa à Instituição - ROBERTA KATLEN FUSCO MARRA - UFRJ