Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/108321
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Baptista, Salete J. | - |
dc.contributor.author | Silva, Maria M. C. | - |
dc.contributor.author | Moroni, Elisabetta | - |
dc.contributor.author | Meli, Massimiliano | - |
dc.contributor.author | Colombo, Giorgio | - |
dc.contributor.author | Dinis, Teresa C. P. | - |
dc.contributor.author | Salvador, Jorge A. R. | - |
dc.date.accessioned | 2023-08-24T09:21:24Z | - |
dc.date.available | 2023-08-24T09:21:24Z | - |
dc.date.issued | 2017 | - |
dc.identifier.issn | 1932-6203 | pt |
dc.identifier.uri | https://hdl.handle.net/10316/108321 | - |
dc.description.abstract | PARP-1 inhibition has been studied over the last decades for the treatment of various diseases. Despite the fact that several molecules act as PARP-1 inhibitors, a reduced number of compounds are used in clinical practice. To identify new compounds with a discriminatory PARP-1 inhibitory function, explicit-solvent molecular dynamics simulations using different inhibitors bound to the PARP-1 catalytic domain were performed. The representative structures obtained were used to generate structure-based pharmacophores, taking into account the dynamic features of receptor-ligand interactions. Thereafter, a virtual screening of compound databases using the pharmacophore models obtained was performed and the hits retrieved were subjected to molecular docking-based scoring. The drug-like molecules featuring the best ranking were evaluated for their PARP-1 inhibitory activity and IC50 values were calculated for the top scoring docked compounds. Altogether, three new PARP-1 inhibitor chemotypes were identified. | pt |
dc.language.iso | eng | pt |
dc.relation | Universidade de Coimbra | pt |
dc.relation | SFRH/ BD/80975/2011 | pt |
dc.relation | AIRC through project IG 15420 | pt |
dc.relation | REEQ/481/QUI/ 2006 | pt |
dc.relation | RECI/QEQ-QFI/0168/2012 | pt |
dc.relation | CENTRO-07- CT62-FEDER-002012 | pt |
dc.rights | openAccess | pt |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt |
dc.subject.mesh | Catalytic Domain | pt |
dc.subject.mesh | Databases, Pharmaceutical | pt |
dc.subject.mesh | Humans | pt |
dc.subject.mesh | Ligands | pt |
dc.subject.mesh | Molecular Docking Simulation | pt |
dc.subject.mesh | Molecular Dynamics Simulation | pt |
dc.subject.mesh | Poly (ADP-Ribose) Polymerase-1 | pt |
dc.subject.mesh | Protein Binding | pt |
dc.subject.mesh | Structure-Activity Relationship | pt |
dc.subject.mesh | Models, Molecular | pt |
dc.title | Novel PARP-1 Inhibitor Scaffolds Disclosed by a Dynamic Structure-Based Pharmacophore Approach | pt |
dc.type | article | - |
degois.publication.firstPage | e0170846 | pt |
degois.publication.issue | 1 | pt |
degois.publication.title | PLoS ONE | pt |
dc.peerreviewed | yes | pt |
dc.identifier.doi | 10.1371/journal.pone.0170846 | pt |
degois.publication.volume | 12 | pt |
dc.date.embargo | 2017-01-01 | * |
uc.date.periodoEmbargo | 0 | pt |
item.grantfulltext | open | - |
item.cerifentitytype | Publications | - |
item.languageiso639-1 | en | - |
item.openairetype | article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.fulltext | Com Texto completo | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.researchunit | CQC - Coimbra Chemistry Centre | - |
crisitem.author.parentresearchunit | Faculty of Sciences and Technology | - |
crisitem.author.orcid | 0000-0002-1938-4150 | - |
crisitem.author.orcid | 0000-0001-6350-5741 | - |
crisitem.author.orcid | 0000-0003-0779-6083 | - |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais FFUC- Artigos em Revistas Internacionais |
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File | Description | Size | Format | |
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Novel-PARP1-Inhibitor-scaffolds-disclosed-by-a-dynamic-structurebased-pharmacophore-approachPLoS-ONE.pdf | 5.08 MB | Adobe PDF | View/Open |
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