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Article: 5-N-methylated quindoline derivatives as telomeric G-quadruplex stabilizing ligands: Effects of 5-N positive charge on quadruplex binding affinity and cell proliferation

Title5-N-methylated quindoline derivatives as telomeric G-quadruplex stabilizing ligands: Effects of 5-N positive charge on quadruplex binding affinity and cell proliferation
Authors
Issue Date2008
PublisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/jmc
Citation
Journal Of Medicinal Chemistry, 2008, v. 51 n. 20, p. 6381-6392 How to Cite?
AbstractA series of 5-N-methyl quindoline (cryptolepine) derivatives (2a-x) as telomeric quadruplex ligands was synthesized and evaluated. The designed ligands possess a positive charge at the 5-N position of the aromatic quindoline scaffold. The quadruplex binding of these compounds was evaluated by circular dichroism (CD) spectroscopy, fluorescence resonance energy transfer (FRET) melting assay, polymerase chain reaction (PCR) stop assay, nuclear magnetic resonance (NMR), and molecular modeling studies. Introduction of a positive charge not only significantly improved the binding ability but also induced the selectivity toward antiparallel quadruplex, whereas the nonmethylated derivatives tended to stabilize hybrid-type quadruplexes. NMR and molecular modeling studies revealed that the ligands stacked on the external G-quartets and the positively charged 5-N atom could contribute to the stabilizing ability. Long-term exposure of human cancer cells to 2r showed a remarkable cessation in population growth and cellular senescence phenotype and accompanied by a shortening of the telomere length. © 2008 American Chemical Society.
Persistent Identifierhttp://hdl.handle.net/10722/168337
ISSN
2015 Impact Factor: 5.589
2015 SCImago Journal Rankings: 2.529
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLu, YJen_US
dc.contributor.authorOu, TMen_US
dc.contributor.authorTan, JHen_US
dc.contributor.authorHou, JQen_US
dc.contributor.authorShao, WYen_US
dc.contributor.authorPeng, Den_US
dc.contributor.authorSun, Nen_US
dc.contributor.authorWang, XDen_US
dc.contributor.authorWu, WBen_US
dc.contributor.authorBu, XZen_US
dc.contributor.authorHuang, ZSen_US
dc.contributor.authorMa, DLen_US
dc.contributor.authorWong, KYen_US
dc.contributor.authorGu, LQen_US
dc.date.accessioned2012-10-08T03:17:46Z-
dc.date.available2012-10-08T03:17:46Z-
dc.date.issued2008en_US
dc.identifier.citationJournal Of Medicinal Chemistry, 2008, v. 51 n. 20, p. 6381-6392en_US
dc.identifier.issn0022-2623en_US
dc.identifier.urihttp://hdl.handle.net/10722/168337-
dc.description.abstractA series of 5-N-methyl quindoline (cryptolepine) derivatives (2a-x) as telomeric quadruplex ligands was synthesized and evaluated. The designed ligands possess a positive charge at the 5-N position of the aromatic quindoline scaffold. The quadruplex binding of these compounds was evaluated by circular dichroism (CD) spectroscopy, fluorescence resonance energy transfer (FRET) melting assay, polymerase chain reaction (PCR) stop assay, nuclear magnetic resonance (NMR), and molecular modeling studies. Introduction of a positive charge not only significantly improved the binding ability but also induced the selectivity toward antiparallel quadruplex, whereas the nonmethylated derivatives tended to stabilize hybrid-type quadruplexes. NMR and molecular modeling studies revealed that the ligands stacked on the external G-quartets and the positively charged 5-N atom could contribute to the stabilizing ability. Long-term exposure of human cancer cells to 2r showed a remarkable cessation in population growth and cellular senescence phenotype and accompanied by a shortening of the telomere length. © 2008 American Chemical Society.en_US
dc.languageengen_US
dc.publisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/jmcen_US
dc.relation.ispartofJournal of Medicinal Chemistryen_US
dc.subject.meshAlkaloids - Chemical Synthesis - Chemistry - Pharmacologyen_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshCell Proliferation - Drug Effectsen_US
dc.subject.meshCell-Free Systemen_US
dc.subject.meshCircular Dichroismen_US
dc.subject.meshDialysisen_US
dc.subject.meshEnzyme Inhibitors - Chemical Synthesis - Chemistry - Pharmacologyen_US
dc.subject.meshG-Quadruplexesen_US
dc.subject.meshHumansen_US
dc.subject.meshIndoles - Chemical Synthesis - Chemistry - Pharmacologyen_US
dc.subject.meshLigandsen_US
dc.subject.meshMethylationen_US
dc.subject.meshModels, Molecularen_US
dc.subject.meshPotassium - Chemistryen_US
dc.subject.meshQuinolines - Chemical Synthesis - Chemistry - Pharmacologyen_US
dc.subject.meshStructure-Activity Relationshipen_US
dc.subject.meshTelomerase - Antagonists & Inhibitors - Metabolismen_US
dc.subject.meshTelomere - Chemistry - Geneticsen_US
dc.subject.meshThermodynamicsen_US
dc.title5-N-methylated quindoline derivatives as telomeric G-quadruplex stabilizing ligands: Effects of 5-N positive charge on quadruplex binding affinity and cell proliferationen_US
dc.typeArticleen_US
dc.identifier.emailMa, DL:edmondma@hku.hken_US
dc.identifier.authorityMa, DL=rp00760en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1021/jm800497pen_US
dc.identifier.pmid18821749-
dc.identifier.scopuseid_2-s2.0-54549117013en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-54549117013&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume51en_US
dc.identifier.issue20en_US
dc.identifier.spage6381en_US
dc.identifier.epage6392en_US
dc.identifier.isiWOS:000260102700014-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridLu, YJ=12040358800en_US
dc.identifier.scopusauthoridOu, TM=9739783500en_US
dc.identifier.scopusauthoridTan, JH=36007787000en_US
dc.identifier.scopusauthoridHou, JQ=10141704500en_US
dc.identifier.scopusauthoridShao, WY=18038932200en_US
dc.identifier.scopusauthoridPeng, D=36875200500en_US
dc.identifier.scopusauthoridSun, N=36841801100en_US
dc.identifier.scopusauthoridWang, XD=9637362400en_US
dc.identifier.scopusauthoridWu, WB=16644397900en_US
dc.identifier.scopusauthoridBu, XZ=8944601100en_US
dc.identifier.scopusauthoridHuang, ZS=8405746100en_US
dc.identifier.scopusauthoridMa, DL=7402075538en_US
dc.identifier.scopusauthoridWong, KY=7404760030en_US
dc.identifier.scopusauthoridGu, LQ=24341268900en_US

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