Banca de QUALIFICAÇÃO: LEONARDO ARAUJO SILVA

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : LEONARDO ARAUJO SILVA
DATE: 17/03/2021
TIME: 15:00
LOCAL: Apresentação remota, via aplicativo
TITLE:

Synthesis of donepezil analogs and their evaluation as acetylcholinesterase inhibitors: A study of alternatives for the treatment of Alzheimer's disease

KEY WORDS:

neurodegenerative diseases, cholinesterase inhibitors, isatins, N-benzyl-piperidines.

PAGES: 19
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUBÁREA: Química Orgânica
SPECIALTY: Síntese Orgânica
SUMMARY:

With the advancement of science and its ability to prolong human life, the society faced some new problems, among them, Alzheimer's disease. One of the main hallmarks of Alzheimer's disease in its early stages is the loss of memory, however, with time, much more severe complications reach those affected by it. This disease, which each year affects a greater number of people in the world, still has no cure, but it has some treatment for their symptoms. Donepezil is the most widely used drug in the world for the treatment of Alzheimer's disease and its main mechanism of action is the inhibition of the enzyme acetylcholinesterase. This enzyme is responsible for the hydrolysis of the neurotransmitter acetylcholine, whose deficit is associated with memory loss. There are no drugs that promote proven regression of the disease and, therefore, the treatments available focus on the combating symptoms. Although treatment with donepezil has an good efficacy to combat symptoms. The scientific community continues to seek new acetylcholinesterase inhibiting agents to be applied in this type of drug therapy. Our research proposal is based on the structure of donepezil for planning three series of new inhibitors with promising activit. We plan to make structural modifications on indolinones, with emphasis on isatin. Some isatin derivatives already demonstrated great acetylcholinesterase inhibitory potential, some of them with greater
percentage of enzyme inhibition, under the evaluated conditions, than donepezil itself. the fraction of donepezil that structurally resembles isatin is the indanone nucleus. There are few studies in the literature exploring the hybridization of isatin with N-benzylpiperidine, which motivates the execution of this project. In this work we will seek thedevelopment of new derivatives of isatin and two other indolinones, indole-2-ona and indol-3-one, in order to mimic the structure of donepezil. For this, the core N-benzylpiperidine will be coupled to the structure of these three compounds, with variations between they in the substituents of the aromatic ring of the indolinone nucleus, generating a total of 70 unpublished mimetic products of donepezil. The ability of these compounds to inhibit acetylcholinesterase enzyme will be evaluated using the spectrophotometric method of
Ellman.

BANKING MEMBERS:
Presidente - 1220404 - CARLOS MAURICIO RABELLO DE SANT ANNA
Interno - 1735975 - CEDRIC STEPHAN GRAEBIN
Interna - 1177598 - ROSANE NORA CASTRO
Externa ao Programa - 1545840 - LUCIA HELENA PINTO DA SILVA
Externo ao Programa - 386960 - WELLINGTON DA SILVA CORTES