title: Synthesis of new lipoic acid conjugates and evaluation of their free radical scavenging and neuroprotective activities.
abstract: A series of new lipoic acid derivatives were designed and synthesized as multitarget ligands against Alzheimer's disease. In particular, analogues combining both lipoic acid and cysteine core structures were synthesized. The antioxidant properties of these compounds were evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS(•+) ) radical cation scavenging assays and ferrous ion chelation. The antioxidant potential of the synthesized compounds was also evaluated in a cellular context and compared to α-lipoic acid and its reduced form, dihydrolipoic acid. The antioxidant effects observed for these compounds in vitro confirmed the importance of free thiol functions for effective antioxidant capacities. However, these promising in vitro results were not mirrored by the antioxidant activity in T67 cell line. This suggests that multiple factors are at stake and warrant further investigations.
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, Via Belmeloro 6 and Via Irnerio 4, 40126, Bologna, Italy.
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Bolognesi
authors.forename: Christian
authors.initials: C
authors.lastname: Bergamini
authors.forename: Romana
authors.initials: R
authors.lastname: Fato
authors.forename: Joël
authors.initials: J
authors.lastname: Oiry
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Vasseur
authors.forename: Michael
authors.initials: M
authors.lastname: Smietana
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016166:Free Radical Scavengers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D008063:Thioctic Acid; C015144:dihydrolipoic acid
keywords: Alzheimer's disease; antioxidant; ferrous chelation; lipoic acid; multitarget ligands