Banca de DEFESA: THIAGO MOREIRA PEREIRA
Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.DISCENTE : THIAGO MOREIRA PEREIRA
DATA : 20/09/2018
HORA: 10:00
LOCAL: Sala 50
TÍTULO:
SYNTHESIS AND PHARMACOLOGICAL EVALUATION OF NEW HYBRID CUMARINIC DERIVATIVES PLANNED AS THERANOSTIC PROTOTYPES FOR ALZHEIMER'S DISEASE
PALAVRAS-CHAVES:
Alzheimer, coumarin, fluorescence, theranostic, hybridization.
PÁGINAS: 138
GRANDE ÁREA: Ciências Exatas e da Terra
ÁREA: Química
SUBÁREA: Química Orgânica
ESPECIALIDADE: Síntese Orgânica
RESUMO:
Alzheimer disease (AD) is a common neurodegenerative disease and is considered the most common form of dementia. According to ONU, due to increase in life expectancy of the world population, the number of people with dementia will grow, achieving 82 million in 2030 and 152 million in 2050. Therefore, AD is considered an important public health problem.
Between the main pathological mechanisms involved in the characteristics lesions of DA studied are protein TAU hiperfosforilation, Ab aggregation, neurovascular disfunction, inflammatory process, oxidative stress, cellular cycle alterations and mitochondrial disfunction. The knowledge of these disturbances has lead to development of drugs with symptomatic effects, approved in many countries, but these drugs act only on the behavioral state, however, advances in the research of pathogenic of AD also has lead to potential disease modifying agents in clinical trials.
Another approach with pharmacokinetic/dynamic and exams of molecular image give rise to the theranostics. This approach of treatment for AD includes therapeutic properties and diagnosis, in only one prototype, with the aim of optimizing the efficacy of drug therapy. In this context of compounds which can act as diagnosis sensor, coumarins show to be an excellent prototype of theranostic agents due to luminescence properties and the large number of pharmacological activities.
Coumarins are natural products widely found in nature and which has an important effect in plants physiology. In the literature, there are many examples of coumarins used for treat AD and as optical sensors of metals applied in biological medium.
The objective of this work comprises the planning of hybrids coumarins fluorescents which can act as theranostic for AD. Two coumarin series were synthesized and fully characterized. The first series of compounds (CCM) was synthesized by two different protocols of synthesis. Five compounds were selected (59b-e,i) and its photophysical characterization in methanol and water was evaluated. Additionally, the compounds 59a-b showed the ability to act as Zn2+ probe in these same solvents.
The second series (HM) was synthesized in four steps, and the compounds 60a-b and 59a-b showed excellent values of inhibitory activities against AChE (12,94nM-128,28nM), very similar to drug Donezepil (6,55nM). The hybrid 60a was still evaluated for the capacity to binding Zn2+ in water (pH = 7,4), validating the propose of this work to produce hybrids which can act as theranostic for AD.
MEMBROS DA BANCA:
Presidente - 1700480 - ARTHUR EUGEN KUMMERLE
Externo à Instituição - FERNANDO DE CARVALHO DA SILVA - UFF
Interno - 1058758 - MARCO EDILSON FREIRE DE LIMA
Externo à Instituição - MARIA LETÍCIA DE CASTRO BARBOSA - UFRJ
Interno - 1979542 - RENATA BARBOSA LACERDA