RT Journal Article
T1 Neurogenic and neuroprotective donepezil-flavonoid hybrids with sigma-1 affinity and inhibition of key enzymes in Alzheimer's disease
A1 Estrada Valencia, Martín
A1 Herrera Arozamena, Clara
A1 Andrés Gordo, Lucía de
A1 Pérez, Concepción
A1 Morales García, José A.
A1 Pérez Castillo, Ana
A1 Ramos, Eva
A1 Romero, Alejandro
A1 Viña Castelao, María Dolores
A1 Yáñez Jato, Matilde
A1 Laurini, Erik
A1 Pricl, Sabrina
A1 Rodríguez Franco, María Isabel
K1 Donepezil-flavonoid hybrids
K1 Neurogenesis
K1 Neuroprotection
K1 Sigma receptors
K1 Human acetylcholinesterase
K1 Human 5-lipoxygenase
K1 Human monoamine oxidases
AB In this work we describe neurogenic and neuroprotective donepezil-flavonoidhybrids (DFHs), exhibiting nanomolar affinities for the sigma-1 receptor (s1R) andinhibition of key enzymes in Alzheimer’s disease (AD), such as acetylcholinesterase(AChE), 5-lipoxygenase (5-LOX), and monoamine oxidases (MAOs). In general, newcompounds scavenge free radical species, are predicted to be brain-permeable, andprotect neuronal cells against mitochondrial oxidative stress. N-(2-(1-Benzylpiperidin-4-yl)ethyl)-6,7-dimethoxy-4-oxo-4H-chromene-2-carboxamide (18) is highlighted dueto its interesting biological profile in σ1R, AChE, 5-LOX, MAO-A and MAO-B. Inphenotypic assays, it protects a neuronal cell line against mitochondrial oxidative stressand promotes maturation of neural stem cells into a neuronal phenotype, which couldcontribute to the reparation of neuronal tissues. Molecular modelling studies of 18 inAChE, 5-LOX and s1R revealed the main interactions with these proteins, which willbe further exploited in the optimization of new, more efficient DFHs
PB Elsevier
SN 0223-5234
YR 2018
FD 2018
LK http://hdl.handle.net/10347/32592
UL http://hdl.handle.net/10347/32592
LA eng
NO Martín Estrada Valencia, Clara Herrera-Arozamena, Lucía de Andrés, Concepción Pérez, José A. Morales-García, Ana Pérez-Castillo, Eva Ramos, Alejandro Romero, Dolores Viña, Matilde Yáñez, Erik Laurini, Sabrina Pricl, María Isabel Rodríguez-Franco, Neurogenic and neuroprotective donepezil-flavonoid hybrids with sigma-1 affinity and inhibition of key enzymes in Alzheimer's disease, European Journal of Medicinal Chemistry, Volume 156, 2018, Pages 534-553, ISSN 0223-5234, https://doi.org/10.1016/j.ejmech.2018.07.026.
NO Financial supports from the Spanish Ministry of Economy, Industry, and Competitiveness (MEICOM, grant SAF2015-64948-C2-1-R to MIRF; grant SAF2014-52940-R to APC), Consejo Superior de Investigaciones Científicas (CSIC, grant PIE-201580E109 to MIRF), and Dirección General de Investigación e Innovación de la Comunidad de Madrid (DGII-CM, grant B2017/BMD-3827, acronym NRF24AD-CM to MIRF) are gratefully acknowledged. DV thanks financial support from the Consellería de Cultura, Educación e Ordenación Universitaria, Centro Singular de Investigación de Galicia and the European Regional Development Fund (ERDF) (accreditation 2016–2019, ED431G/05). MEV and CH-A thank their Ph.D. fellowships from COLCIENCIAS (Colombia) and MEC (FPU16/01704, Spain), respectively.
DS Minerva
RD 28 abr 2026