dc.creator | Matos, Ana M. de | es |
dc.creator | Martins, Alice | es |
dc.creator | Man,Teresa | es |
dc.creator | Evans, David | es |
dc.creator | Walter, Magnus | es |
dc.creator | Oliveira, Maria Conceição | es |
dc.creator | López López, Óscar | es |
dc.creator | Fernández-Bolaños Guzmán, José María | es |
dc.creator | Rauter, Amélia P. | es |
dc.date.accessioned | 2019-08-23T10:21:32Z | |
dc.date.available | 2019-08-23T10:21:32Z | |
dc.date.issued | 2019 | |
dc.identifier.citation | Matos, A.M.d., Martins, A., Man, e., Evans, D., Walter, M., Oliveira, M.C.,...,Rauter, A.P. (2019). Design and Synthesis of CNS-targeted Flavones and Analogues with Neuroprotective Potential Against H2O2- and Aβ1-42-Induced Toxicity in SH-SY5Y Human Neuroblastoma Cells. Pharmaceuticals, 12 (2), 98. | |
dc.identifier.issn | 1424-8247 | es |
dc.identifier.uri | https://hdl.handle.net/11441/88624 | |
dc.description.abstract | With the lack of available drugs able to prevent the progression of Alzheimer’s disease (AD), the discovery of new neuroprotective treatments able to rescue neurons from cell injury is presently a matter of extreme importance and urgency. Here, we were inspired by the widely reported potential of natural flavonoids to build a library of novel flavones, chromen-4-ones and their C-glucosyl derivatives, and to explore their ability as neuroprotective agents with suitable pharmacokinetic profiles. All compounds were firstly evaluated in a parallel artificial membrane permeability assay (PAMPA) to assess their effective permeability across biological membranes, namely the blood-brain barrier (BBB). With this test, we aimed not only at assessing if our candidates would be well-distributed, but also at rationalizing the influence of the sugar moiety on the physicochemical properties. To complement our analysis, logD7.4 was determined. From all screened compounds, the p-morpholinyl flavones stood out for their ability to fully rescue SH-SY5Y human neuroblastoma cells against both H2O2- and Aβ1-42-induced cell death. Cholinesterase inhibition was also evaluated, and modest inhibitory activities were found. This work highlights the potential of C-glucosylflavones as neuroprotective agents, and presents the p-morpholinyl C-glucosylflavone 37, which did not show any cytotoxicity towards HepG2 and Caco-2 cells at 100 μM, as a new lead structure for further development against AD. | es |
dc.description.sponsorship | Fundação para a Ciência e a Tecnologia-UID/Multi/0612/2019 | es |
dc.description.sponsorship | Unión Europea-D3i4AD), FP7-PEOPLE-2013-IAPP, GA 612347 | es |
dc.format | application/pdf | es |
dc.language.iso | eng | es |
dc.publisher | MDPI | es |
dc.relation.ispartof | Pharmaceuticals, 12 (2), 98. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Alzheimer’s disease | es |
dc.subject | Aβ1-42 | es |
dc.subject | cholinesterase inhibitors | es |
dc.subject | flavones | es |
dc.subject | chromen-4-ones | es |
dc.subject | C-glucosyl flavonoids | es |
dc.subject | PAMPA | es |
dc.title | Design and Synthesis of CNS-targeted Flavones and Analogues with Neuroprotective Potential Against H2O2- and Aβ1-42-Induced Toxicity in SH-SY5Y Human Neuroblastoma Cells | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Química orgánica | es |
dc.relation.projectID | UID/Multi/0612/2019 | es |
dc.relation.projectID | D3i4AD), FP7-PEOPLE-2013-IAPP, GA 612347 | es |
dc.relation.publisherversion | https://doi.org/10.3390/ph12020098 | es |
dc.identifier.doi | 10.3390/ph12020098 | es |
idus.format.extent | 18 p. | es |
dc.journaltitle | Pharmaceuticals | es |
dc.publication.volumen | 12 | es |
dc.publication.issue | 2 | es |
dc.publication.initialPage | 98 | es |