Herrera-Arozamena C

References (4)

Title : New flavonoid - N,N-dibenzyl(N-methyl)amine hybrids: Multi-target-directed agents for Alzheimer s disease endowed with neurogenic properties - Estrada-Valencia_2019_J.Enzyme.Inhib.Med.Chem_34_712
Author(s) : Estrada-Valencia M , Herrera-Arozamena C , Perez C , Vina D , Morales-Garcia JA , Perez-Castillo A , Ramos E , Romero A , Laurini E , Pricl S , Rodriguez-Franco MI
Ref : J Enzyme Inhib Med Chem , 34 :712 , 2019
Abstract : The design of multi-target directed ligands (MTDLs) is a valid approach for obtaining effective drugs for complex pathologies. MTDLs that combine neuro-repair properties and block the first steps of neurotoxic cascades could be the so long wanted remedies to treat neurodegenerative diseases (NDs). By linking two privileged 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. They were subjected to biological evaluation in a battery of targets involved in Alzheimer's disease (AD) and other NDs, namely human cholinesterases (hAChE/hBuChE), beta-secretase (hBACE-1), monoamine oxidases (hMAO-A/B), lipoxygenase-5 (hLOX-5) and sigma receptors (sigma1R/sigma2R). After a funnel-type screening, 6,7-dimethoxychromone - DBMA (6) was highlighted due to its neurogenic properties and an interesting MTD-profile in hAChE, hLOX-5, hBACE-1 and sigma1R. Molecular dynamic simulations showed the most relevant drug-protein interactions of hybrid 6, which could synergistically contribute to neuronal regeneration and block neurodegeneration.
ESTHER : Estrada-Valencia_2019_J.Enzyme.Inhib.Med.Chem_34_712
PubMedSearch : Estrada-Valencia_2019_J.Enzyme.Inhib.Med.Chem_34_712
PubMedID: 31852270

Title : Neurogenic and neuroprotective donepezil-flavonoid hybrids with sigma-1 affinity and inhibition of key enzymes in Alzheimer's disease - Estrada_2018_Eur.J.Med.Chem_156_534
Author(s) : Estrada Valencia M , Herrera-Arozamena C , de Andres L , Perez C , Morales-Garcia JA , Perez-Castillo A , Ramos E , Romero A , Vina D , Yanez M , Laurini E , Pricl S , Rodriguez-Franco MI
Ref : Eur Journal of Medicinal Chemistry , 156 :534 , 2018
Abstract : In this work we describe neurogenic and neuroprotective donepezil-flavonoid hybrids (DFHs), exhibiting nanomolar affinities for the sigma-1 receptor (sigma1R) and inhibition of key enzymes in Alzheimer's disease (AD), such as acetylcholinesterase (AChE), 5-lipoxygenase (5-LOX), and monoamine oxidases (MAOs). In general, new compounds scavenge free radical species, are predicted to be brain-permeable, and protect 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 due to its interesting biological profile in sigma1R, AChE, 5-LOX, MAO-A and MAO-B. In phenotypic assays, it protects a neuronal cell line against mitochondrial oxidative stress and promotes maturation of neural stem cells into a neuronal phenotype, which could contribute to the reparation of neuronal tissues. Molecular modelling studies of 18 in AChE, 5-LOX and sigma1R revealed the main interactions with these proteins, which will be further exploited in the optimization of new, more efficient DFHs.
ESTHER : Estrada_2018_Eur.J.Med.Chem_156_534
PubMedSearch : Estrada_2018_Eur.J.Med.Chem_156_534
PubMedID: 30025348

Title : New cinnamic - N-benzylpiperidine and cinnamic - N,N-dibenzyl(N-methyl)amine hybrids as Alzheimer-directed multitarget drugs with antioxidant, cholinergic, neuroprotective and neurogenic properties - Estrada_2016_Eur.J.Med.Chem_121_376
Author(s) : Estrada M , Herrera-Arozamena C , Perez C , Vina D , Romero A , Morales-Garcia JA , Perez-Castillo A , Rodriguez-Franco MI
Ref : Eur Journal of Medicinal Chemistry , 121 :376 , 2016
Abstract : Here we describe new families of multi-target directed ligands obtained by linking antioxidant cinnamic-related structures with N-benzylpiperidine (NBP) or N,N-dibenzyl(N-methyl)amine (DBMA) fragments. Resulting hybrids, in addition to their antioxidant and neuroprotective properties against mitochondrial oxidative stress, are active at relevant molecular targets in Alzheimer's disease, such as cholinesterases (hAChE and hBuChE) and monoamine oxidases (hMAO-A and hMAO-B). Hybrids derived from umbellic - NBP (8), caffeic - NBP (9), and ferulic - DBMA (12) displayed balanced biological profiles, with IC50s in the low-micromolar and submicromolar range for hChEs and hMAOs, and an antioxidant potency comparable to vitamin E. Moreover, the caffeic - NBP hybrid 9 is able to improve the differentiation of adult SGZ-derived neural stem cells into a neuronal phenotype in vitro.
ESTHER : Estrada_2016_Eur.J.Med.Chem_121_376
PubMedSearch : Estrada_2016_Eur.J.Med.Chem_121_376
PubMedID: 27267007

Title : Novel tacrine-grafted ugi adducts as multipotent anti-Alzheimer drugs: a synthetic renewal in tacrine-ferulic Acid hybrids - Benchekroun_2015_ChemMedChem_10_523
Author(s) : Benchekroun M , Bartolini M , Egea J , Romero A , Soriano E , Pudlo M , Luzet V , Andrisano V , Jimeno ML , Lopez MG , Wehle S , Gharbi T , Refouvelet B , de Andres L , Herrera-Arozamena C , Monti B , Bolognesi ML , Rodriguez-Franco MI , Decker M , Marco-Contelles J , Ismaili L
Ref : ChemMedChem , 10 :523 , 2015
Abstract : Herein we describe the design, multicomponent synthesis, and biological, molecular modeling and ADMET studies, as well as in vitro PAMPA-blood-brain barrier (BBB) analysis of new tacrine-ferulic acid hybrids (TFAHs). We identified (E)-3-(hydroxy-3-methoxyphenyl)-N-{8[(7-methoxy-1,2,3,4-tetrahydroacridin-9-yl)am ino]octyl}-N-[2-(naphthalen-2-ylamino)2-oxoethyl]acrylamide (TFAH 10 n) as a particularly interesting multipotent compound that shows moderate and completely selective inhibition of human butyrylcholinesterase (IC50 =68.2 nM), strong antioxidant activity (4.29 equiv trolox in an oxygen radical absorbance capacity (ORAC) assay), and good beta-amyloid (Abeta) anti-aggregation properties (65.6 % at 1:1 ratio); moreover, it is able to permeate central nervous system (CNS) tissues, as determined by PAMPA-BBB assay. Notably, even when tested at very high concentrations, TFAH 10 n easily surpasses the other TFAHs in hepatotoxicity profiling (59.4 % cell viability at 1000 muM), affording good neuroprotection against toxic insults such as Abeta1-40 , Abeta1-42 , H2 O2 , and oligomycin A/rotenone on SH-SY5Y cells, at 1 muM. The results reported herein support the development of new multipotent TFAH derivatives as potential drugs for the treatment of Alzheimer's disease.
ESTHER : Benchekroun_2015_ChemMedChem_10_523
PubMedSearch : Benchekroun_2015_ChemMedChem_10_523
PubMedID: 25537267