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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Copper (II) and zinc (II) complexes with flavanone derivatives: Identification of potential cholinesterase inhibitors by on-flow assays

Texto completo
Autor(es):
Franceschini Sarria, Andre Lucio ; Lopes Vilela, Adriana Ferreira ; Frugeri, Barbara Mammana ; Fernandes, Joao Batista ; Carlos, Rose Maria ; das Gracas Fernandes da Silva, Maria Fatima ; Cass, Quezia Bezerra ; Cardoso, Carmen Lucia
Número total de Autores: 8
Tipo de documento: Artigo Científico
Fonte: Journal of Inorganic Biochemistry; v. 164, p. 141-149, NOV 2016.
Citações Web of Science: 3
Resumo

Metal chelates strongly influence the nature and magnitude of pharmacological activities in flavonoids. In recent years, studies have shown that a promising class of flavanone-metal ion complexes can act as selective cholinesterase inhibitors (ChEls), which has led our group to synthesize a new series of flavanone derivatives (hesperidin, hesperetin, naringin, and naringenin) complexed to either copper (II) or zinc (II) and to evaluate their potential use as selective ChEIs. Most of the synthesized complexes exhibited greater inhibitory activity against acetylcholinesterase (AChE) than against butyrylcholinesterase (BChE). Nine of these complexes constituted potent, reversible, and selective ChEls with inhibitory potency (IC50) and inhibitory constant (K-1) ranging from 0.02 to 4.5 mu M. Copper complexes with flavanone-bipyridine derivatives afforded the best inhibitory activity against AChE and BChE. The complex Cu(naringin)(2,2'-bipyridine) (11) gave IC50 and K-i values of 0.012 +/- 0.002 and 0.07 +/- 0.01 mu M for huAChE, respectively, which were lower than the inhibitory values obtained for standard galanthamine (IC50 = 206 +/- 30.0 and K-1 = 126 +/- 18.0 mu M). Evaluation of the inhibitory activity of this complex against butyrylcholinesterase from human serum (huBChE) gave IC50 and Ki values of 8.0 +/- 1.4 and 2.0 +/- 0.1 mu M, respectively. A Liquid Chromatography-Immobilized Capillary Enzyme Reactor by UV detection (LC-ICER-UV) assay allowed us to determine the IC50 and K-1 values and the type of mechanism for the best inhibitors. (C) 2016 Elsevier Inc. All rights reserved. (AU)

Processo FAPESP: 09/01847-1 - Obtenção de inseticida e fungicida contra formigas cortadeiras e seu fungo simbionte em Myracrodruon urundeuva e de complexos de coordenação com metais de compostos ativos para controle desta praga
Beneficiário:André Lúcio Franceschini Sarria
Linha de fomento: Bolsas no Brasil - Doutorado Direto
Processo FAPESP: 13/07600-3 - CIBFar - Centro de Inovação em Biodiversidade e Fármacos
Beneficiário:Glaucius Oliva
Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
Processo FAPESP: 06/58043-3 - Controle de formigas cortadeiras, estudos integrados
Beneficiário:João Batista Fernandes
Linha de fomento: Auxílio à Pesquisa - Temático