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

Author(s)

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

• Document type: Journal article
• Source: Journal of Inorganic Biochemistry; v. 164, p. 141-149, NOV 2016.
• Web of Science Citations: 3

Abstract

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)

• FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
• Grantee: Glaucius Oliva
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 06/58043-3 - Leaf cutting ants control, integrated studies
• Grantee: João Batista Fernandes
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 09/01847-1 - Attainment of insecticide, fungicide against leaf cutting ants and their symbiotic fungi from Myracrodruon urundeuva and of coordination complex of metals with bioactive compounds for the control of this plague
• Grantee: André Lúcio Franceschini Sarria
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)