Fine-tuning the neuroprotective and blood-brain barrier permeability profile of multi-target agents designed to prevent progressive mitochondrial dysfunction
MetadataShow full item record
Alzheimer's disease is an irreversible, complex and progressive neurodegenerative disorder associated with oxidative stress and mitochondrial dysfunction. Exogenous antioxidants can be beneficial for decreasing oxidative stress, as they are able to reward the lack of efficacy of the endogenous defense systems and raise the overall antioxidant response in a pathological condition. Along our overarching project related with the design and development of potent and safe multi-target mitochondriotropic antioxidants, based on dietary antioxidants, novel derivatives were obtained. Overall, mitochondriotropic antioxidants showed remarkable antioxidant and chelating properties, presenting low cytotoxic effects on human differentiated neuronal (SH-SY5Y) and hepatocarcinoma (HepG2) cells and exhibited neuroprotective properties on SH-SY5Y cells against 6-hydroxydopamine (6-OHDA) or hydrogen peroxide (H2O2) oxidative insults. Moreover, compounds 58, 59, 62, 63, 66 and 67 were able to permeate a layer of hCMEC/D3 cells in a time-dependent manner. Mitochondriotropic antioxidant 67 stands out by its remarkable iron chelating and neuroprotective properties toward both H2O2 and 6-OHDA-induced oxidative damage, drug-like properties and BBB permeability. © 2019 Elsevier Masson SAS
Showing items related by title, author, creator and subject.
Multi-target-directed ligands for Alzheimer's disease: Discovery of chromone-based monoamine oxidase/cholinesterase inhibitors (2020) Reis J.; Cagide F.; Valencia M.E.; Teixeira J.; Bagetta D.; Pérez C.; Uriarte E.; Oliveira P.J.; Ortuso F.; Alcaro S.; ... (Elsevier Masson SAS, 2018)
Pathophysiology of blood-brain barrier in brain injury in cold and hot environments: Novel drug targets for neuroprotection (2020) Sharma H.S.; Muresanu D.F.; Lafuente J.V.; Nozari A.; Patnaik R.; Skaper S.D.; Sharma A. (Bentham Science Publishers B.V., 2016)
PEGylated PLGA Nanoparticles As a Smart Carrier to Increase the Cellular Uptake of a Coumarin-Based Monoamine Oxidase B Inhibitor (2020) Fernandes C.; Martins C.; Fonseca A.; Nunes R.; Matos M.J.; Silva R.; Garrido J.; Sarmento B.; Remião F.; Otero-Espinar F.J.; ... (American Chemical Society, 2018)