Luminescent Ru(II) Phenanthroline Complexes as a Probe for Real-Time Imaging of Aβ Self-Aggregation and Therapeutic Applications in Alzheimer's Disease.
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•radical. Luminescence using fluorescence lifetime imaging (FLIM) enables real-time imaging of the conformational changes of the self-aggregation of Aβ with incubation of complexes (0-24 h) in phosphate buffer at micromolar concentrations. By this technique, we identified protofibrills in the self-assembly of Aβ1-40and globular structures in the short fragment Aβ15-21in aqueous solution.
Departamento de Química, Universidade Federal de São Carlos , São Carlos, São Paulo 13565-905, Brazil.
Debora E S
DE
Silva
Departamento de Química, Universidade Federal de São Carlos , São Carlos, São Paulo 13565-905, Brazil.
Mariana P
MP
Cali
Departamento de Física, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, USP , Ribeirão Preto, São Paulo 14040-901, Brazil.
Wallance M
WM
Pazin
Departamento de Biofísica, Escola Paulista de Medicina, Universidade Federal de São Paulo , São Paulo, São Paulo 04023-062, Brazil.
Estevão
E
Carlos-Lima
Departamento de Química Orgânica e Inorgânica, Universidade Federal do Ceará , Ceará Fortaleza, 60451-970, Brazil.
Maria Teresa
MT
Salles Trevisan
Departamento de Química, Universidade Federal de São Carlos , São Carlos, São Paulo 13565-905, Brazil.
Tiago
T
Venâncio
Departamento de Biofísica, Escola Paulista de Medicina, Universidade Federal de São Paulo , São Paulo, São Paulo 04023-062, Brazil.
Manoel
M
Arcisio-Miranda
Departamento de Física, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, USP , Ribeirão Preto, São Paulo 14040-901, Brazil.
Amando S
AS
Ito
Departamento de Química, Universidade Federal de São Carlos , São Carlos, São Paulo 13565-905, Brazil.
Rose M
RM
Carlos
D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000201:enzymology; D016229:Amyloid beta-Peptides / Q000032:analysis*; D000818:Animals; D002091:Butyrylcholinesterase / Q000378:metabolism; D002460:Cell Line; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D004593:Electrophorus; D006801:Humans; D049408:Luminescent Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D061848:Optical Imaging / Q000379:methods*; D010618:Phenanthrolines / Q000737:chemistry / Q000494:pharmacology*; D066329:Protein Aggregates; D012428:Ruthenium / Q000737:chemistry / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D002800:Cholinesterase Inhibitors; D049408:Luminescent Agents; D010618:Phenanthrolines; D066329:Protein Aggregates; D012428:Ruthenium; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase