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Authordc.contributor.authorNoureini, Sakineh Kazemi 
Authordc.contributor.authorKheirabadi, Mitra 
Authordc.contributor.authorMasoumi, Fatima 
Authordc.contributor.authorKhosrogerdi, Farve 
Authordc.contributor.authorZarei, Younes 
Authordc.contributor.authorSuárez Rozas, Cristian 
Authordc.contributor.authorSalas Norambuena, Julio 
Authordc.contributor.authorCassels Niven, Bruce
Cita de ítemdc.identifier.citationInternational Journal of Molecular Sciences Volumen: 19 Número: 4 Número de artículo: 1239es_ES
Abstractdc.description.abstractTelomerase, the enzyme responsible for cell immortality, is an important target in anti-cancer drug discovery. Boldine, an abundant aporphine alkaloid of Peumus boldus, is known to inhibit telomerase at non-toxic concentrations. Cytotoxicity of N-benzylsecoboldine hydrochloride (BSB), a synthetic derivative of boldine, was determined using the MTT method in MCF7 and MDA-MB231 cells. Aliquots of cell lysates were incubated with various concentrations of BSB in qTRAP (quantitative telomere repeat amplification protocol)-ligand experiments before substrate elongation by telomerase or amplification by hot-start Taq polymerase. The crystal structure of TERT, the catalytic subunit of telomerase from Tribolium castaneum, was used for docking and molecular dynamics analysis. The qTRAP-ligand data gave an IC50 value of about 0.17 +/- 0.1 mu M for BSB, roughly 400 times stronger than boldine, while the LD50 in the cytotoxicity assays were 12.5 and 21.88 mu M, respectively, in cells treated for 48 h. Although both compounds interacted well with the active site, MD analysis suggests a second binding site with which BSB interacts via two hydrogen bonds, much more strongly than boldine. Theoretical analyses also evaluated the IC50 for BSB as submicromolar. BSB, with greater hydrophobicity and flexibility than boldine, represents a promising structure to inhibit telomerase at non-toxic concentrations.es_ES
Patrocinadordc.description.sponsorshipHakim Sabzevari University FONDECYT Grant 1150868es_ES
Type of licensedc.rightsAttribution-NonCommercial-NoDerivs 3.0 Chile*
Link to Licensedc.rights.uri*
Sourcedc.sourceInternational Journal of Molecular Scienceses_ES
Keywordsdc.subjectTelomerase inhibitiones_ES
Keywordsdc.subjectBinding sitees_ES
Títulodc.titleTelomerase inhibition by a new synthetic derivative of the aporphine alkaloid boldinees_ES
Document typedc.typeArtículo de revista
Indexationuchile.indexArtículo de publicación ISIes_ES

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Attribution-NonCommercial-NoDerivs 3.0 Chile
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 3.0 Chile