Toward a rational design of multitarget-directed antioxidants: merging memoquin and lipoic acid molecular frameworks.
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.
Bolognesi
Maria Laura
ML
Department of Pharmaceutical Sciences, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy. marialaura.bolognesi@unibo.it
Cavalli
Andrea
A
Bergamini
Christian
C
Fato
Romana
R
Lenaz
Giorgio
G
Rosini
Michela
M
Bartolini
Manuela
M
Andrisano
Vincenza
V
Melchiorre
Carlo
C
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
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