Banca de DEFESA: ROMARIO JONAS DE OLIVEIRA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : ROMARIO JONAS DE OLIVEIRA
DATE: 29/06/2023
TIME: 08:00
LOCAL: Departamento de Química
TITLE:

Design, Molecular Docking, Synthesis, Signaling and Biological Activity of Z-Systems (Enine and Enedine) Coupled to a Heterocyclic Ring.

KEY WORDS:

Unsaturated systems; vinyl tellurides; heterocyclic compounds; docking molecular; antineoplastic activity.

PAGES: 138
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUBÁREA: Química Orgânica
SPECIALTY: Síntese Orgânica
SUMMARY:

Cancer is one of the main comorbidities faced by humanity, especially breast and colorectal adenocarcinoma, with an increasingly frequent number of cases. This raises the need for planning new chemotherapy, and chemistry involving polyunsaturated systems incorporated into heterocyclic systems can be an interesting alternative. Thus, the aim of this work is to study the preparation and antineoplastic potential of heterocyclic polyunsaturated systems against different tumor cell lines. For this purpose, vinylic telluride containing an ester moiety (compound 5, 70% yield) was synthesized as a precursor. The preparation of the heterocyclic moiety was started through the synthesis of different arylamidoximes (compounds 2a-j, 55-93% yield). The studies of the coupling reaction for the formation of the Z enine portion were unfortunately not effective. However, important intermediates were obtained, compounds 10, 11, 13 and 16 (78, 89, 95 and 60% yield, respectively). The molecular docking study was conducted using the PARP-1 enzyme (PDB ID:5DS3) as active site, while the evaluation of the antitumor activity of the compounds was carried out against the MCF-7 and Caco-2 tumor cell lines. Molecular docking studies, as well as the antitumor evaluation, indicated compound 21a as a potential PARP-1 inhibitor when compared to the other compounds, with binding energy equal to -7,07 kcal.mol-1 and antitumor activity 0,323 mM for MCF-7 and 0,399 mM for Caco-2. Additionally, compound 21c showed a high level of selectivity for the healthy VERO cell, and may be used in future studies with a greater variety of tumor cell lines, aiming at the development of a possible drug candidate.

COMMITTEE MEMBERS:
Presidente - ***.451.424-** - JULIANO CARLO RUFINO DE FREITAS - UFCG
Interno - JOAO RUFINO DE FREITAS FILHO
Interno - MARCILIO MARTINS DE MORAES
Externo à Instituição - ANDRE AUGUSTO PIMENTEL LIESEN NASCIMENTO
Externa à Instituição - JOANA MARIA DE FARIAS BARROS