title: Toward a rational design of multitarget-directed antioxidants: merging memoquin and lipoic acid molecular frameworks.
abstract: Novel multitargeted antioxidants 3-6 were designed by combining the antioxidant features, namely, a benzoquinone fragment and a lipoyl function, of two multifunctional lead candidates. They were then evaluated to determine their profile against Alzheimer's disease. They showed antioxidant activity, improved following enzymatic reduction, in mitochondria and T67 cell line. They also displayed a balanced inhibitory profile against amyloid-beta aggregation and acetylcholinesterase, emerging as promising molecules for neuroprotectant lead discovery.
authors.affiliation: Department of Pharmaceutical Sciences, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy. marialaura.bolognesi@unibo.it
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Bolognesi
authors.forename: Andrea
authors.initials: A
authors.lastname: Cavalli
authors.forename: Christian
authors.initials: C
authors.lastname: Bergamini
authors.forename: Romana
authors.initials: R
authors.lastname: Fato
authors.forename: Giorgio
authors.initials: G
authors.lastname: Lenaz
authors.forename: Michela
authors.initials: M
authors.lastname: Rosini
authors.forename: Manuela
authors.initials: M
authors.lastname: Bartolini
authors.forename: Vincenza
authors.initials: V
authors.lastname: Andrisano
authors.forename: Carlo
authors.initials: C
authors.lastname: Melchiorre
mesh_terms: D000473:Alkanes / Q000737:chemistry*; D000544:Alzheimer Disease / Q000378:metabolism / Q000517:prevention & control / Q000628:therapy; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000975:Antioxidants / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015195:Drug Design; D004579:Electron Transport; D005021:Ethylamines / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D011485:Protein Binding / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013367:Submitochondrial Particles / Q000187:drug effects / Q000378:metabolism; D008063:Thioctic Acid / Q000737:chemistry*; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000473:Alkanes; D016229:Amyloid beta-Peptides; D000975:Antioxidants; D005021:Ethylamines; D008024:Ligands; D017382:Reactive Oxygen Species; C521476:memoquin; D014451:Ubiquinone; D008063:Thioctic Acid; C003741:ubiquinol