Banca de QUALIFICAÇÃO: LUCAS DIEGO PEREIRA BENTO

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : LUCAS DIEGO PEREIRA BENTO
DATE: 19/02/2025
TIME: 14:00
LOCAL: https://meet.google.com/dcb-tpqp-mtk
TITLE:

Synthesis and characterization of ZINC390718 analogues as agents against Alzheimer's disease

KEY WORDS:

Alzheimer's disease, Acetylcholinesterase, Butyrylcholinesterase, Dibenzaloketones

PAGES: 31
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUBÁREA: Química Orgânica
SUMMARY:

Alzheimer's disease (AD) is a progressive neurodegenerative disorder resulting from a natural change in brain chemistry, when there is a failure in the processing of beta-amyloid protein by the central nervous system. Then, poorly hydrolyzed and toxic protein residues appear between neurons. Because of this toxicity, neurons progressively deteriorate and symptoms occur. Acetylcholinesterase (AChE) is found abundantly in the central nervous system (CNS) and is expressed by neurons in skeletal muscles and in the erythrocyte membrane, while Butyrylcholinesterase (BuChE) is associated with glial cells and is found mainly in blood plasma 2 . During the development of AD, AChE levels in the CNS decrease, while BuChE activity progressively increases and, consequently, BuChE mainly controls the regulation of acetylcholine. Recent studies have evaluated the in vitro effect of ZINC390718 on both cholinesterases, after being previously selected using computational approaches such as molecular dynamics to understand the binding mode of this compound within the cholinesterase enzymes. The first objective of this work was to synthesize dibenzalacetones (DBAs) due to their structural similarity to ZINC390718 through aldol condensation between acetone and substituted aromatic aldehydes and then reduce them to 1,5-diphenylpentan-3-ones. Simultaneously, theoretical calculations of the interaction of the proposed molecules with the targets AChE and BuChE were performed. Theoretical calculations showed that the DBAs presented better activity than their reduced products. This resulted in a second objective, where acetone was replaced by cyclohexanone to increase the rigidity of the structures. New calculations were performed and it was found that these DBAs derived from cyclohexanone presented greater interaction with the targets. Several DBAs were evaluated for their enzymatic activities against AChE and BuChE and demonstrated relevant inhibitory capacity. The synthesized products had their structures elucidated by 1H and 13C Nuclear Magnetic Resonance (NMR), melting point and infrared (IR) spectroscopy.

BANKING MEMBERS:
Externo à Instituição - THIAGO MOREIRA PEREIRA
Externo ao Programa - 953.035.100-34 - DANIEL LUCIANO FALKOSKI - SVI