Luminescent Ru(II) Phenanthroline Complexes as a Probe for Real-Time Imaging of A beta Self-Aggregation and Therapeutic Applications in Alzheimer's Disease

Author(s)

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.

• Document type: Journal article
• Source: Journal of Medicinal Chemistry; v. 59, n. 19, p. 9215-9227, OCT 13 2016.
• Web of Science Citations: 7

Abstract

The complexes, cis-{[}Ru(phen)(2)(Apy)(2)](2+), Apy = 4-aminopyridine and 3,4-aminopyridine, are stable in aqueous solution with strong visible absorption. They present emission in the visible region with long lifetime that accumulates in the cytoplasm of Neuro2A cell line without appreciable cytotoxicity. The complexes also serve as mixed-type reversible inhibitors of human AChE and BuChE with high active Site contact. cis-{[}Ru(phen)(2)(3,4Apy)(2)](2+) competes efficiently with DMPO by the OH center dot radical. Luminescence using fluorescence lifetime imaging (FLIM) enables real-time imaging of the onformational Changes of the self-aggregation, of A beta with incubation of complexes (0-24 h) in phosphate buffer at micromolar concentrations. By this technique, we identified protofibrillsin the self-assembly of A beta(1-40) and globular structures in the short fragment A beta(15-21) in aqueous solution. (AU)

• FAPESP's process: 12/02065-0 - Electrophysiology of antimicrobial peptides in planar lipid bilayers
• Grantee: Manoel de Arcisio Miranda Filho
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/26895-7 - Heterogeneities in lipids and proteins structures: studies by advanced fluorescence techniques
• Grantee: Amando Siuiti Ito
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/07935-8 - Multifunctional transition metal complexes to treatment and diagnosis of Alzheimer's Disease
• Grantee: Débora Eduarda Soares Silva
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 14/12538-8 - Development of luminescent transition metal complexes to recognize and map in real time the aggregation processes of the B-amyloid peptide and of tau protein and to investigate the antioxidant and acetylcholinesterase enzyme inhibition activity
• Grantee: Rose Maria Carlos
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/24643-0 - Electrophysiological analysis of gating mechanisms of Inward-rectifier potassium ion channels (Kir)
• Grantee: Estêvão Carlos Lima
• Support Opportunities: Scholarships in Brazil - Scientific Initiation