title: Combined in Vitro Cell-Based/in Silico Screening of Naturally Occurring Flavonoids and Phenolic Compounds as Potential Anti-Alzheimer Drugs.
abstract: Alzheimer's disease (AD) is the main cause of dementia in people over 65 years. One of the major culprits in AD is the self-aggregation of amyloid-β peptide (Aβ), which has stimulated the search for small molecules able to inhibit Aβ aggregation. In this context, we recently reported a simple, but effective in vitro cell-based assay to evaluate the potential antiaggregation activity of putative Aβ aggregation inhibitors. In this work this assay was used together with docking and molecular dynamics simulations to analyze the anti-Aβ aggregation activity of several naturally occurring flavonoids and phenolic compounds. The results showed that rosmarinic acid, melatonin, and o-vanillin displayed zero or low inhibitory capacity, curcumin was found to have an intermediate inhibitory potency, and apigenin and quercetin showed potent antiaggregation activity. Finally, the suitability of the combined in vitro cell-based/in silico approach to distinguish between active and inactive compounds was further assessed for an additional set of flavonols and dihydroflavonols.
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology and Physical-Chemistry, School of Pharmacy, and Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona , E-08028, Barcelona, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Espargaró
authors.affiliation: Department of Nutrition, Food Sciences, and Gastronomy, School of Pharmacy and Institute of Biomedicine, Campus Torribera, University of Barcelona , Prat de la Riba 171, E-08921, Santa Coloma de Gramenet, Spain.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Ginex
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology and Physical-Chemistry, School of Pharmacy, and Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona , E-08028, Barcelona, Spain.
authors.forename: Maria Del Mar
authors.initials: MD
authors.lastname: Vadell
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology and Physical-Chemistry, School of Pharmacy, and Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona , E-08028, Barcelona, Spain.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Busquets
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology and Physical-Chemistry, School of Pharmacy, and Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona , E-08028, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Estelrich
authors.affiliation: Laboratory of Pharmaceutical Chemistry (CSIC Associated Unit), School of Pharmacy, and Institute of Biomedicine (IBUB), University of Barcelona , E-08028, Barcelona, Spain.
authors.forename: Diego
authors.identifier: 0000-0002-8140-8555
authors.initials: D
authors.lastname: Muñoz-Torrero
authors.affiliation: Department of Nutrition, Food Sciences, and Gastronomy, School of Pharmacy and Institute of Biomedicine, Campus Torribera, University of Barcelona , Prat de la Riba 171, E-08921, Santa Coloma de Gramenet, Spain.
authors.forename: F Javier
authors.identifier: 0000-0002-8049-3567
authors.initials: FJ
authors.lastname: Luque
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology and Physical-Chemistry, School of Pharmacy, and Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona , E-08028, Barcelona, Spain.
authors.forename: Raimon
authors.identifier: 0000-0003-3894-2362
authors.initials: R
authors.lastname: Sabate
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors*; D016564:Amyloid beta-Protein Precursor; D047310:Apigenin / Q000737:chemistry; D001547:Benzaldehydes / Q000737:chemistry; D002934:Cinnamates / Q000737:chemistry; D053630:Depsides / Q000737:chemistry; D005419:Flavonoids / Q000737:chemistry*; D006801:Humans; D066298:In Vitro Techniques; D015394:Molecular Structure; D010446:Peptide Fragments / Q000737:chemistry; D010636:Phenols / Q000737:chemistry*; D011794:Quercetin / Q000737:chemistry / Q000494:pharmacology*; D000097123:Rosmarinic Acid
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D047310:Apigenin; D001547:Benzaldehydes; D002934:Cinnamates; D053630:Depsides; D005419:Flavonoids; D010446:Peptide Fragments; D010636:Phenols; D011794:Quercetin; D000097123:Rosmarinic Acid; C545487:APP protein, human; C060843:2-vanillin