Multifunctional transition metal complexes to treatment and diagnosis of Alzheimer's Disease

• Grant number: 14/07935-8
• Support Opportunities: Scholarships in Brazil - Master
• Start date: July 01, 2014
• End date: February 29, 2016
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Rose Maria Carlos
• Grantee: Débora Eduarda Soares Silva
• Host Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil

Abstract

In this project we intend to develop luminescent transition metal complexes of the type cis-[Ru(a-diimina)2(Apy)2]2+, Apy= 4-aminopyridine and 3,4-aminopyridine to diagnosis and treatment of Alzheimer's Disease (AD). AD is a progressive neurodegenerative disease that causes injury in the memory and cognitive function of elderly. The misfolding of amyloid-b (Ab-1-42) into oligomers and fibrils and acumulation into plaques in the brain represent the pathological characteristics of AD. The current medicines for AD are dominated by drugs developed to treat the symptoms of dementia, particularly the acetylcholinesterase enzyme inhibitors. Aminopyridines protect the neuronal cells by preventing neurotoxicity caused by excitatory effects as hypoxia and excitatory disfunction and act in many different intracellular targets including acetylcholinesterase enzyme inhibition, oxidative stress and calcium disfunction. The therapeutic effects of complexes proposed in this work will be evaluated by the changes in the luminescence response of complex with the neurotoxicity induced on the Ab-1-42, i.e., by the inhibition ability of complex against the aggregation of Ab-1-42. The enzymatic inhibition activity of complex against the acetylcholinesterase enzyme and in the oxidative stress caused by the reactive oxygen species will also be investigated. The complexes proposed in this work are convenient due to feasibility of synthesis, thermal stability and strong luminescence sensitive to changes in the medium. (AU)

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)

SILVA, DEBORA E. S.; CALI, MARIANA P.; PAZIN, WALLANCE M.; CARLOS-LIMA, ESTEVAO; SALLES TREVISAN, MARIA TERESA; VENANCIO, TIAGO; ARCISIO-MIRANDA, MANOEL; ITO, AMANDO S.; CARLOS, ROSE M.. Luminescent Ru(II) Phenanthroline Complexes as a Probe for Real-Time Imaging of A beta Self-Aggregation and Therapeutic Applications in Alzheimer's Disease. Journal of Medicinal Chemistry, v. 59, n. 19, p. 9215-9227, OCT 13 2016. (12/02065-0, 14/26895-7, 14/07935-8, 14/12538-8, 14/24643-0)