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)

Vilela, Adriana F. L. ; Frugeri, Barbara M. ; Sarria, Andre L. F. ; Kitamura, Rodrigo O. S. ; Fernandes, Joao B. ; Silva, Maria F. G. F. ; Cass, Quezia B. ; Cardoso, Carmen L.

• Document type: Journal article
• Source: Journal of the Brazilian Chemical Society; v. 27, n. 3, p. 12-pg., 2016-03-01.

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 (K-i) ranging from 1.24 to 11.5 mu mol (L-1). One of the compounds was particularly promising, showing IC50 and Ki values of 1.24 +/- 0.01 and 1.06 +/- 0.01 mu mol L-1, respectively, for huAChE. These values were lower than those for the standard inhibitor galanthamine (IC50 = 206 +/- 30.0 and K-1 = 126 +/- 18.0 mu mol 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: 13/01710-1 - Enzyme ligand: new models of screening
• Grantee: Quezia Bezerra Cass
• Support Opportunities: Research Projects - Thematic Grants
• 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: 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 Opportunities: Scholarships in Brazil - Doctorate (Direct)
• 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 Opportunities: Scholarships in Brazil - Master