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dc.contributor.authorTang, Yonges_ES
dc.contributor.authorRodríguez-Salarichs, Javieres_ES
dc.contributor.authorEstévez Gallego, J.es_ES
dc.contributor.authorBalaguer, Francisco de Asíses_ES
dc.contributor.authorRedondo-Horcajo, Marianoes_ES
dc.contributor.authorLucena-Agell, Danieles_ES
dc.contributor.authorBarasoain, Isabeles_ES
dc.contributor.authorDíaz, José Fernandoes_ES
dc.contributor.authorFang, Wei-shuo S.es_ES
dc.date.accessioned2017-07-20T10:04:20Z-
dc.date.available2017-07-20T10:04:20Z-
dc.date.issued2017-06-03-
dc.identifier.citationEur J Med Chem. 137:488-503 (2017)-
dc.identifier.issn0223-5234-
dc.identifier.urihttp://hdl.handle.net/10261/153329-
dc.description53 p.-6 fig.-3 tab.-1 graf. Tang, Yong et al.es_ES
dc.description.abstractIn our efforts to improve the efficacy of taxane-based microtubule (MT) stabilizing agents against tumor drug resistance mediated by multiple mechanisms, two clinically relevant factors were focused: i.e., P-glycoprotein and βIII-tubulin overexpression. Based on the structure of C-seco taxoid 1 m (IDN5390) which was believed to more selectively interact with βIII-tubulin than paclitaxel, we prepared a series of C-seco taxoids bearing various 7,9-O-linkages and/or different substituents at C2 and C3′ positions. Some of them exhibited much more potent binding affinity to MTs and cytotoxicity than their C-seco parent compounds in drug resistant cells with both mechanisms. SAR analysis indicated that C2 modifications significantly enhanced MT binding but brought ambiguous influence to cytotoxicity whereas 7,9-linkage and C3′ modifications enhance cytotoxicity more efficiently than improve MT binding. These observations illustrate a better translation of molecular binding effect to cellular activity by C ring closure and C3′ modification than C2 modification in C-seco taxoids.es_ES
dc.description.sponsorshipThis research was supported by NSFC (Grant No. 30930108) to (W.-S.F.), and by BIPPED2 (S2010/BMD-2457) (J.F.D.), project of the Comunidad de Madrid and the BIO2013-42984R (to J.F.D.) project from the Ministry of Economy and Competitiveness of Spain.es_ES
dc.language.isoenges_ES
dc.publisherElsevieres_ES
dc.relationMINECO/ICTI2013-2016/BIO2013-42984-Res_ES
dc.relation.isversionofPostprintes_ES
dc.rightsopenAccessen_EN
dc.subjectTaxoidses_ES
dc.subjectβIII-tubulines_ES
dc.subjectP-Glycoproteines_ES
dc.subjectDrug resistancees_ES
dc.titleModification of C-seco taxoids through ring tethering and substituent replacement leading to effective agents against tumor drug resistance mediated by βIII-Tubulin and P-glycoprotein (P-gp) overexpressions.es_ES
dc.typeArtículoes_ES
dc.identifier.doi10.1016/j.ejmech.2017.06.001-
dc.description.peerreviewedPeer reviewedes_ES
dc.relation.publisherversionhttp://dx.doi.org/10.1016/j.ejmech.2017.06.001es_ES
dc.identifier.e-issn1768-3254-
dc.embargo.terms2018-06-03es_ES
dc.rights.licensehttp://creativecommons.org/licenses/by-nc-nd/4.0/-
dc.contributor.funderNational Natural Science Foundation of Chinaes_ES
dc.contributor.funderComunidad de Madrides_ES
dc.contributor.funderMinisterio de Economía y Competitividad (España)es_ES
dc.relation.csices_ES
oprm.item.hasRevisionno ko 0 false*
dc.identifier.funderhttp://dx.doi.org/10.13039/501100001809es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100003329es_ES
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