Scholarship 17/13524-9 - Fármacos neuroprotetores, Doença de Alzheimer - BV FAPESP
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Design, synthesis and biological evaluation of new derivatives of LAPDESF FTD-AO and LAPDESF FTD-TAU series with potential activity in the treatment of Alzheimer's Disease

Grant number: 17/13524-9
Support Opportunities:Scholarships abroad - Research Internship - Doctorate
Start date until: November 14, 2017
End date until: May 16, 2018
Field of knowledge:Health Sciences - Pharmacy - Medicines Analysis and Control
Principal Investigator:Chung Man Chin
Grantee:Diego Eidy Chiba
Supervisor: Pui Kai Li
Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Institution abroad: Ohio State University, Columbus, United States  
Associated to the scholarship:16/08470-4 - DESIGN, SYNTHESIS AND BIOLOGICAL EVALUATION OF NEW DERIVATIVES OF LAPDESF FTD-AO AND LAPDESF FTD-TAU SERIES WITH POTENTIAL ACTIVITY IN THE TREATMENT OF ALZHEIMER'S DISEASE, BP.DR

Abstract

Alzheimer's disease (AD) is the main and most common cause of senile dementia, responsable for 50-75% of diagnosed cases. In developed countries, AD is the fourth cause of death, only behind of cardiovascular disease, cancer and stroke. The projection of the World Health Organization (WHO) is that by 2050 the number of elderly will increase 21% in the world. AD is a progressive neurodegenerative disease, in which patients diagnosed show an extensive loss of synapses and neurons in the hippocampus and frontal and temporal cortex, compromising gradually his cognitive functions such as memory, learning ability, thinking, besides of the impairment of communication skills and performance of daily activities. Currently there is no treatment able to cure or modify effectively the disease, only medications (tacrine, donepezil, rivastigmine, galantamine and memantine) that improve some symptoms manifested by patients. It is therefore of great importance to find and develop new therapeutic approaches and new drugs able to delay or prevent the progression of the disease. Because of the described, this project aims to obtain novel drug candidates with anti-inflammatory, neuroprotective and microtubule stabilizing activities, using molecular hybridization of lipoic acid or ferulic acid with phtalimide derivatives. Under pathological conditions, there is an imbalance between the binding of protein tau to MT and resulted in an abnormal increase of free fraction of tau. When tau is phosphorylated in excess, it results in formation of NFT, damaging the connection with MT, and eventually leading to the disassembly, so resulting in neuronal death. Because of this, this project will also evaluate the new compounds obtained and some of the compounds obtained in Brazil (LAPDESF FTD-AO AND LAPDESF FTD-TAU serie) for its capability of stabilizing microtubules in vitro. (AU)

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