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

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Autor(es):
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.
Número total de Autores: 8
Tipo de documento: Artigo Científico
Fonte: Journal of the Brazilian Chemical Society; v. 27, n. 3, p. 12-pg., 2016-03-01.
Resumo

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)

Processo FAPESP: 13/01710-1 - Ligantes enzimáticos: novos modelos de triagem
Beneficiário:Quezia Bezerra Cass
Modalidade de apoio: Auxílio à Pesquisa - Temático
Processo FAPESP: 06/58043-3 - Controle de formigas cortadeiras, estudos integrados
Beneficiário:João Batista Fernandes
Modalidade de apoio: Auxílio à Pesquisa - Temático
Processo FAPESP: 07/07196-7 - Estudo fitoquímico biomonitorado de Picramnia bahiensis e Thyrsodium schomburgkianum: obtenção de inseticida, fungicida contra formigas cortadeiras e seu fungo simbionte e microencapsulação de compostos ativos
Beneficiário:Rodrigo Ossamu Saga Kitamura
Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
Processo FAPESP: 07/06393-3 - Obtenção de inseticida, fungicida contra formigas cortadeiras e seu fungo simbionte em Astronium juglandifolium e busca de complexos organometálicos de compostos ativos no controle das formigas cortadeiras
Beneficiário:André Lúcio Franceschini Sarria
Modalidade de apoio: Bolsas no Brasil - Mestrado