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https://hdl.handle.net/10316/108321
Title: | Novel PARP-1 Inhibitor Scaffolds Disclosed by a Dynamic Structure-Based Pharmacophore Approach | Authors: | Baptista, Salete J. Silva, Maria M. C. Moroni, Elisabetta Meli, Massimiliano Colombo, Giorgio Dinis, Teresa C. P. Salvador, Jorge A. R. |
Issue Date: | 2017 | Project: | Universidade de Coimbra SFRH/ BD/80975/2011 AIRC through project IG 15420 REEQ/481/QUI/ 2006 RECI/QEQ-QFI/0168/2012 CENTRO-07- CT62-FEDER-002012 |
Serial title, monograph or event: | PLoS ONE | Volume: | 12 | Issue: | 1 | 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. | URI: | https://hdl.handle.net/10316/108321 | ISSN: | 1932-6203 | DOI: | 10.1371/journal.pone.0170846 | Rights: | openAccess |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais FFUC- Artigos em Revistas Internacionais |
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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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