RT Journal Article
T1 New flavonoid – N,N-dibenzyl(N-methyl)amine hybrids: Multi-target-directed agents for Alzheimer´s disease endowed with neurogenic properties
A1 Estrada Valencia, Martín
A1 Herrera Arozamena, Clara
A1 Pérez, Concepción
A1 Viña Castelao, María Dolores
A1 Morales García, José A.
A1 Pérez Castillo, Ana
A1 Ramos, Eva
A1 Romero, Alejandro
A1 Laurini, Erik
A1 Prici, Sabrina
A1 Rodríguez Franco, María Isabel
K1 Multi-target-directed ligands
K1 Neurogenesis
K1 Sigma receptors
K1 Human b-secretase
K1 Human lipoxygenase-5
K1 Human cholinesterases
K1 Alzheimer’s disease
K1 Neurodegenerative diseases
AB The design of multi-target directed ligands (MTDLs) is a valid approach for obtaining effective drugs forcomplex pathologies. MTDLs that combine neuro-repair properties and block the first steps of neurotoxiccascades could be the so long wanted remedies to treat neurodegenerative diseases (NDs). By linking twoprivileged scaffolds with well-known activities in ND-targets, the flavonoid and the N,N-dibenzyl(N-methyl)-amine (DBMA) fragments, new CNS-permeable flavonoid – DBMA hybrids (1–13) were obtained. Theywere subjected to biological evaluation in a battery of targets involved in Alzheimer’s disease (AD) andother NDs, namely human cholinesterases (hAChE/hBuChE), b-secretase (hBACE-1), monoamine oxidases(hMAO-A/B), lipoxygenase-5 (hLOX-5) and sigma receptors (r1R/r2R). After a funnel-type screening, 6,7-dimethoxychromone – DBMA (6) was highlighted due to its neurogenic properties and an interestingMTD-profile in hAChE, hLOX-5, hBACE-1 and r1R. Molecular dynamic simulations showed the most relevant drug-protein interactions of hybrid 6, which could synergistically contribute to neuronal regenerationand block neurodegeneration.
PB Taylor & Francis
SN 1475-6366
YR 2019
FD 2019
LK http://hdl.handle.net/10347/21198
UL http://hdl.handle.net/10347/21198
LA eng
NO Martín Estrada-Valencia, Clara Herrera-Arozamena, Concepción Pérez, Dolores Viña, José A. Morales-García, Ana Pérez-Castillo, Eva Ramos, Alejandro Romero, Erik Laurini, Sabrina Pricl & María Isabel Rodríguez-Franco (2019). New flavonoid – N,N-dibenzyl(N-methyl)amine hybrids: Multi-target-directed agents for Alzheimer's disease endowed with neurogenic properties, Journal of Enzyme Inhibition and Medicinal Chemistry, 34:1, 712-727
NO The authors gratefully acknowledge the following financial supports: Spanish Ministry of Science, Innovation and Universities(grants SAF2015-64948-C2-1-R and RTI2018-093955-B-C21 to MIRF;grant SAF2017-85199-P to APC), Spanish National ResearchCouncil (CSIC, grant PIE-201580E109 to MIRF), General Council forResearch and Innovation of the Community of Madrid andEuropean Structural Funds (grant B2017/BMD-3827 – NRF24ADCM to MIRF), Consellería de Cultura, Educacion e Ordenación Universitaria de Galicia, and the European Regional DevelopmentFund (ERDF) (accreditation 2016–2019, ED431G/05 to DV). EL andSP gratefully acknowledge the support of NVIDIA Corporationwith the donation of the Titan Xp GPU used for this research. MEVand CH-A also thank their PhD fellowships from DepartamentoAdministrativo de Ciencia, Tecnología e Innovacion (COLCIENCIAS,  Colombia) and Spanish Ministry of Education (MEC, grant FPU16/01704), respectively. JAM-G is a fellow from the BiomedicalResearch Networking Centre on Neurodegenerative Diseases(CIBERNED, Spain)
DS Minerva
RD 23 abr 2026