Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/174316
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Purgatorio, Rosario | - |
dc.contributor.author | Gambacorta, Nicola | - |
dc.contributor.author | Catto, Marco | - |
dc.contributor.author | de Candia, Modesto | - |
dc.contributor.author | Pisani, Leonardo | - |
dc.contributor.author | Espargaró Colomé, Alba | - |
dc.contributor.author | Sabaté Lagunas, Raimon | - |
dc.contributor.author | Cellamare, Saverio | - |
dc.contributor.author | Nicolotti, Orazio | - |
dc.contributor.author | Altomare, Cosimo D. | - |
dc.date.accessioned | 2021-02-25T11:22:24Z | - |
dc.date.available | 2021-02-25T11:22:24Z | - |
dc.date.issued | 2020-12-07 | - |
dc.identifier.issn | 1420-3049 | - |
dc.identifier.uri | http://hdl.handle.net/2445/174316 | - |
dc.description.abstract | Thirty-six novel indole-containing compounds, mainly 3-(2-phenylhydrazono) isatins and structurally related 1H-indole-3-carbaldehyde derivatives, were synthesized and assayed as inhibitors of beta amyloid (Aβ) aggregation, a hallmark of pathophysiology of Alzheimer's disease. The newly synthesized molecules spanned their IC50 values from sub- to two-digit micromolar range, bearing further information into structure-activity relationships. Some of the new compounds showed interesting multitarget activity, by inhibiting monoamine oxidases A and B. A cell-based assay in tau overexpressing bacterial cells disclosed a promising additional activity of some derivatives against tau aggregation. The accumulated data of either about ninety published and thirty-six newly synthesized molecules were used to generate a pharmacophore hypothesis of antiamyloidogenic activity exerted in a wide range of potencies, satisfactorily discriminating the 'active' compounds from the 'inactive' (poorly active) ones. An atom-based 3D-QSAR model was also derived for about 80% of 'active' compounds, i.e., those achieving finite IC50 values lower than 100 μM. The 3D-QSAR model (encompassing 4 PLS factors), featuring acceptable predictive statistics either in the training set (n = 45, q2 = 0.596) and in the external test set (n = 14, r2ext = 0.695), usefully complemented the pharmacophore model by identifying the physicochemical features mainly correlated with the Aβ anti-aggregating potency of the indole and isatin derivatives studied herein. | - |
dc.format.extent | 26 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | MDPI | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.3390/molecules25235773 | - |
dc.relation.ispartof | Molecules, 2020, vol. 25(23), num. 5773 | - |
dc.relation.uri | https://doi.org/10.3390/molecules25235773 | - |
dc.rights | cc-by (c) Purgatorio, Rosario et al., 2020 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es | - |
dc.source | Articles publicats en revistes (Farmàcia, Tecnologia Farmacèutica i Fisicoquímica) | - |
dc.subject.classification | Malaltia d'Alzheimer | - |
dc.subject.classification | Compostos heterocíclics | - |
dc.subject.classification | Pèptids | - |
dc.subject.classification | Agregació (Química) | - |
dc.subject.other | Alzheimer's disease | - |
dc.subject.other | Heterocyclic compounds | - |
dc.subject.other | Peptides | - |
dc.subject.other | Aggregation (Chemistry) | - |
dc.title | Pharmacophore Modeling and 3D-QSAR Study of Indole and Isatin Derivatives as Antiamyloidogenic Agents Targeting Alzheimer's Disease | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 705333 | - |
dc.date.updated | 2021-02-25T11:22:24Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 33297547 | - |
Appears in Collections: | Articles publicats en revistes (Farmàcia, Tecnologia Farmacèutica i Fisicoquímica) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
705333.pdf | 12.6 MB | Adobe PDF | View/Open |
This item is licensed under a
Creative Commons License