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Planning, synthesis and pharmacological evaluation of hybrid compounds with potential activity in the treatment of Alzheimer's Disease

Grant number: 13/23461-3
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): March 01, 2014
Effective date (End): September 05, 2017
Field of knowledge:Health Sciences - Pharmacy - Medicines Analysis and Control
Principal Investigator:Chung Man Chin
Grantee:Rafael Consolin Chelucci
Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Alzheimer's disease (AD) is clearly the main and most common cause of senile dementia in the world contributing with 60-70% of diagnosed cases. Being the fourth leading cause of death in developed countries, DA is behind only cardiovascular disease, cancer and stroke. Worldwide, the prevalence of dementia is estimated in 3.9 % of people aged 60 or more. In developed countries, about one in ten elderly aged 65 years or more has some degree of dementia, while more than a third of people considered to be very old, with more than 85 years, show some symptoms and signs of dementia. AD is a progressive brain disease, and diagnosed patients show an extensive loss of synapses and neurons in the hippocampus and in the frontal and temporal cortices, which gradually compromise their memory, learning ability, reasoning, communication and activities of daily living. Currently there is no cure or treatment that can effectively modify the disease, and the drugs available on the market (tacrine, donepezil, rivastigmine, galantamine and memantine) only reduce some symptoms manifested by patients. Thus, it is essential to develop new therapeutic approaches for obtaining new drugs that can slow or prevent disease progression. This work aims to obtain drug candidates with anti-inflammatory/neuroprotective properties, obtained by molecular hybridization strategy, where the inhibition of TNF-±, the stabilizing action of microtubules and donation of nitric oxide, could reduce the process of neuroinflammation associated with deposition of senile plaques and neurofibrillary tangles, reducing oxidative stress and contributing to synaptic plasticity, cognition and memory, attenuating the effects associated with loss of neurons of patients affected by AD. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
CHELUCCI, RAFAEL C.; DE OLIVEIRA, ISABELA J.; BARBIERI, KARINA P.; LOPES-PIRES, MARIA E.; POLESI, MARISA C.; CHIBA, DIEGO E.; CARLOS, IRACILDA Z.; MARCONDES, SISI; DOS SANTOS, JEAN L.; CHUNG, MANCHIN. Antiplatelet activity and TNF- release inhibition of phthalimide derivatives useful to treat sickle cell anemia. MEDICINAL CHEMISTRY RESEARCH, v. 28, n. 8, p. 1264-1271, . (15/19531-1, 13/23461-3)

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