Aminonaphthoquinone Mannich Bases Derived from Lawsone and Their Copper(II) Complex Derivatives: Synthesis and Potential Cholinesterase Inhibitors as Identified by On-flow Assay

Author(s)

Adriana F. L. Vilela ^[1] ; Bárbara M. Frugeri ^[2] ; André L. F. Sarria ^[3] ; Rodrigo O. S. Kitamura ^[4] ; João B. Fernandes ^[5] ; Maria F. G. F. Silva ^[6] ; Quezia B. Cass ^[7] ; Carmen L. Cardoso ^[8]

Affiliation

^[1] Universidade de São Paulo. Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto - Brasil

^[2] Universidade de São Paulo. Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto - Brasil

^[3] Universidade Federal de São Carlos. Departamento de Química - Brasil

^[4] Universidade Federal de São Carlos. Departamento de Química - Brasil

^[5] Universidade Federal de São Carlos. Departamento de Química - Brasil

^[6] Universidade Federal de São Carlos. Departamento de Química - Brasil

^[7] Universidade Federal de São Carlos. Departamento de Química - Brasil

^[8] Universidade de São Paulo. Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto - Brasil

• Document type: Journal article
• Source: Journal of the Brazilian Chemical Society; v. 27, n. 3, p. 534-545, 2016-03-00.

Abstract

A new series of Mannich bases derived from 2-hydroxy-1,4-naphthoquinone (lawsone), substituted benzaldehydes and two primary amines, and their Cu2+ complexes were synthesized and evaluated for their potential as selective cholinesterase inhibitors (ChEIs). Immobilized capillary enzyme reactors (ICERs) bearing butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) were used not only for the on-flow screening assay but also for determining the inhibitory potency and equilibrium binding constants of the lead inhibitors. Eight copper complexes were identified and characterized as potent reversible and selective ChEIs with inhibitory potencies (IC50) and constants of inhibition (Ki) ranging from 1.24 to 11.5 µmol L-1. One of the compounds was particularly promising, showing IC50 and Ki values of 1.24 ± 0.01 and 1.06 ± 0.01 µmol L-1, respectively, for huAChE. These values were lower than those for the standard inhibitor galanthamine (IC50 = 206 ± 30.0 and Ki = 126 ± 18.0 µmol L-1). Even though, it is showing noncompetitive inhibition of huAChE and linear mixed-type inhibition of eeAChE. These complexes showed a promising cholinesterase inhibitory activity and can be used as model inhibitors. (AU)

• FAPESP's process: 07/06393-3 - Obtention of insecticide, fungitoxic against leaf-cutting ants and its simbiont fungus in Astronium juglandifolium and search for organometallic complexes of active compounds to leaf-cutting ants control
• Grantee: André Lúcio Franceschini Sarria
• Support type: Scholarships in Brazil - Master
• FAPESP's process: 13/01710-1 - Enzyme ligand: new models of screening
• Grantee: Quezia Bezerra Cass
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 07/07196-7 - Biomonitored phytochemical study of Picramnia bahiensis and Thyrsodium schomburgkianum: obtaining insecticide, fungicide against leaf-cutting ants and their symbiotic fungi and micro-encapsulation of active compounds
• Grantee: Rodrigo Ossamu Saga Kitamura
• Support type: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 06/58043-3 - Leaf cutting ants control, integrated studies
• Grantee: João Batista Fernandes
• Support type: Research Projects - Thematic Grants