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Design, Synthesis, and Evaluation of 2,9-Bis[(substituted-aminomethyl)phenyl]-1,10-phenanthroline Derivatives as G-Quadruplex Ligands.

hal.structure.identifierAcides Nucléiques : Régulations Naturelle et Artificielle [ARNA]
dc.contributor.authorGUEDDOUDA, Nassima Meriem
hal.structure.identifierAcides Nucléiques : Régulations Naturelle et Artificielle [ARNA]
dc.contributor.authorHURTADO, Rosales Myanou
hal.structure.identifierAcides Nucléiques : Régulations Naturelle et Artificielle [ARNA]
dc.contributor.authorMOREAU, Stéphane
hal.structure.identifierAcides Nucléiques : Régulations Naturelle et Artificielle [ARNA]
dc.contributor.authorRONGA, Luisa
hal.structure.identifierAcides Nucléiques : Régulations Naturelle et Artificielle [ARNA]
dc.contributor.authorDAS, Rabindra Nath
hal.structure.identifierAcides Nucléiques : Régulations Naturelle et Artificielle [ARNA]
dc.contributor.authorSAVRIMOUTOU, Solène
hal.structure.identifierAcides Nucléiques : Régulations Naturelle et Artificielle [ARNA]
dc.contributor.authorRUBIO, Sandra
hal.structure.identifierAcides Nucléiques : Régulations Naturelle et Artificielle [ARNA]
dc.contributor.authorMARCHAND, Adrien
hal.structure.identifierAcides Nucléiques : Régulations Naturelle et Artificielle [ARNA]
dc.contributor.authorMENDOZA, Oscar
hal.structure.identifierInstitut de Chimie de la Matière Condensée de Bordeaux [ICMCB]
dc.contributor.authorMARCHIVIE, Mathieu
hal.structure.identifierAcides Nucléiques : Régulations Naturelle et Artificielle [ARNA]
dc.contributor.authorELMI, Lilian
hal.structure.identifierAcides Nucléiques : Régulations Naturelle et Artificielle [ARNA]
dc.contributor.authorCHANSAVANG, Albain
hal.structure.identifierCellules souches hématopoïétiques normales et leucémiques
dc.contributor.authorDESPLAT, Vanessa
hal.structure.identifierAcides Nucléiques : Régulations Naturelle et Artificielle [ARNA]
dc.contributor.authorGABELICA, Valérie
hal.structure.identifierAcides Nucléiques : Régulations Naturelle et Artificielle [ARNA]
dc.contributor.authorBOURDONCLE, Anne
hal.structure.identifierAcides Nucléiques : Régulations Naturelle et Artificielle [ARNA]
dc.contributor.authorMERGNY, Jean
hal.structure.identifierAcides Nucléiques : Régulations Naturelle et Artificielle [ARNA]
dc.contributor.authorGUILLON, Jean
dc.date.issued2017-01-20
dc.identifier.issn1860-7179
dc.description.abstractEnGenomic sequences able to form guanine quadruplexes (G4) are found in oncogene promoters, in telomeres, and in 5'- and 3'-untranslated regions as well as introns of messenger RNAs. These regions are potential targets for drugs designed to treat cancer. Herein, we present the design and syntheses of ten new phenanthroline derivatives and characterization of their interactions with G4-forming oligonucleotides. We evaluated ligand-induced stabilization and specificity and selectivity of ligands for various G4 conformations using FRET-melting experiments. We investigated the interaction of compound 1 a (2,9-bis{4-[(3-dimethylaminopropyl)aminomethyl]phenyl}-1,10-phenanthroline), which combined the greatest stabilizing effect and specificity for G4, with human telomeric sequences using FRET, circular dichroism, and ESI-MS. In addition, we showed that compound 1 a interferes with the G4 helicase activity of Saccharomyces cerevisiae Pif1. Interestingly, compound 1 a was significantly more cytotoxic toward two human leukemic cell lines than to normal human blood mononuclear cells. These novel phenanthroline derivatives will be a starting point for further development and optimization of potent G4 ligands that have potential as anticancer agents.
dc.description.sponsorshipSynthèse et évaluation cellulaire de ligands spécifiques de G-quadruplexes dérivés de porphyrines et salens - ANR-12-BSV8-0008
dc.language.isoen
dc.publisherWiley-VCH Verlag
dc.subject.encircular dichroism
dc.subject.enphenanthroline
dc.subject.enG-quadruplexes
dc.subject.enG4 ligands
dc.subject.enG-quadruplex
dc.subject.enhelicase assay
dc.subject.enFRET-melting
dc.title.enDesign, Synthesis, and Evaluation of 2,9-Bis[(substituted-aminomethyl)phenyl]-1,10-phenanthroline Derivatives as G-Quadruplex Ligands.
dc.typeArticle de revue
dc.identifier.doi10.1002/cmdc.201600511
dc.subject.halChimie/Matériaux
bordeaux.journalChemMedChem
bordeaux.page146-160
bordeaux.volume12
bordeaux.issue2
bordeaux.peerReviewedoui
hal.identifierhal-01461586
hal.version1
hal.popularnon
hal.audienceInternationale
hal.origin.linkhttps://hal.archives-ouvertes.fr//hal-01461586v1
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