Banca de DEFESA: MARINA BRANDÃO DA FONSECA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : MARINA BRANDÃO DA FONSECA
DATE: 14/11/2024
TIME: 09:00
LOCAL: UFRRJ - PPGQ - Ambiente virtual
TITLE:

MULTICOMPONENT REACTIONS AS A SYNTHETIC STRATEGY FOR THE OBTENTION OF BIOACTIVE HETEROCYCLES.

KEY WORDS:

Acridinones; Quinazolinones; Xanthenediones; Acridinediones

PAGES: 368
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUMMARY:

Multicomponent Reactions (MCRs) are a set of chemical reactions that have as a general concept the synthesis of a single final product with a high degree of chemical diversity from three or more reagents. Various multicomponent reactions are known, with the main ones being the Hantzsch reaction and the Biginelli reaction. The Hantzsch reaction was originally developed for the synthesis of dihydropyridines; however, after modifications, it has also been used for the synthesis of acridinones. The Biginelli reaction originally describes the synthesis of dihydropyrimidinones, but with a change in reagents, it can also be carried out for the synthesis of quinazolinones. This work demonstrates the use of both multicomponent reactions for the synthesis of a diverse range of heterocycles. A total of 17 acridinones and 7 acridinediones were synthesized through a modified methodology of the Hantzsch reaction. Various reagents were used, demonstrating the versatility of the reaction, yielding 8 novel molecules in the literature. The Biginelli reaction was employed in the synthesis of 11 quinazolinones, with two being novel, and 4 xanthenediones, confirmed as byproducts of the Biginelli reaction. Various reagents were used, showcasing how this reaction can be utilized as a tool in the synthesis of heterocycles. Fifteen acridones were evaluated against targets related to Alzheimer’s disease (cholinesterases and antioxidant activity). The molecules mostly demonstrated inhibitory activity against acetylcholinesterase and butyrylcholinesterase, as well as antioxidant properties, while the permeability across the blood-brain barrier was satisfactory for 8 acridones. The quinazolinones were evaluated for their cytotoxic potential and trypanocide activity. The results indicate promising trypanocide activity for molecules containing the 4-bromophenyl group, while the cytotoxic activity was not satisfactory. Seven acridinediones and two acridinones were evaluated using in silico methods for their potential interactions with tubulin; the results allowed for mapping the interactions that occur when using lawsone as a reagent in the reaction, in addition to demonstrating the modification of positioning at the colchicine site when increasing the size of the acridones. Nevertheless, the overall results appear promising from the perspective of exploratory chemistry, with 39 molecules synthesized through multicomponent reactions. The use of multicomponent reactions has proven to be a fast, effective, and versatile method as a synthesis strategy for new bioactive molecules, contributing to future research.

COMMITTEE MEMBERS:
Externo à Instituição - SABRINA BAPTISTA FERREIRA - UFRJ
Presidente - 1735975 - CEDRIC STEPHAN GRAEBIN
Interno - 2624418 - CLAUDIO EDUARDO RODRIGUES DOS SANTOS
Interno - 3292567 - EDUARDO HILLMANN WANDERLIND
Externa à Instituição - ROBERTA KATLEN FUSCO MARRA - UFRJ