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dc.creatorMartínez, Regina-
dc.creatorDi Geronimo Quintero, Bruno-
dc.creatorPastor, Myriam-
dc.creatorZapico Rodríguez, José María-
dc.creatorCoderch Boué, Claire-
dc.creatorPanchuk, Rostyslav-
dc.creatorSkorokhyd, Nadia-
dc.creatorMaslyk, Maciej-
dc.creatorRamos González, Ana-
dc.creatorPascual-Teresa Fernández, Beatriz de-
dc.date2020-
dc.date.accessioned2022-02-15T05:00:18Z-
dc.date.available2022-02-15T05:00:18Z-
dc.date.issued2020-02-15-
dc.identifier000000726407-
dc.identifier.urihttp://hdl.handle.net/10637/13383-
dc.descriptionMolecules, e-ISSN 1420-3049 , 2020, 25, 1497-
dc.description.abstractThe design of multitarget drugs (MTDs) has become an innovative approach for the search of effective treatments in complex diseases such as cancer. In this work, we communicate our efforts in the design of multi-targeting histone deacetylase (HDAC) and protein kinase CK2 inhibitors as a novel therapeutic strategy against cancer. Using tetrabromobenzotriazole (TBB) and 2-dimethylamino-4,5,6,7-tetrabromo-benzimidazole (DMAT) as scaffolds for CK2 inhibition, and a hydroxamate to coordinate the zinc atom present in the active site of HDAC (zinc binding group, ZBG), new multitarget inhibitors have been designed and synthesized. According to the in vitro assays, N-Hydroxy-6-(4,5,6,7-tetrabromo-2-(dimethylamino)-1H-benzo[d]imidazol-1-yl)hexanamide (11b) is the most interesting compound, with IC50 values of 0.66; 1.46 and 3.67 µM. for HDAC6; HDAC1 and CK2; respectively. Cellular assays on different cancer cell lines rendered promising results for N-Hydroxy-8-(4,5,6,7-tetrabromo-2-(dimethylamino)-1H-benzo[d]imidazol-1-yl)octanamide (11d). This inhibitor presented the highest cytotoxic activity, proapoptotic capability, and the best mitochondria-targeting and multidrug-circumventing properties, thus being the most promising drug candidate for further in vivo studies.en_EN
dc.formatapplication/pdf-
dc.language.isoen-
dc.relationThis work was supported by the Spanish MICIU/FEDER, UE grant number RTI2018-093539-B-I00. B. di G, thanks Fundación Universitaria San Pablo CEU for FPI fellowship and the Spanish MINECO for FPU fellowship.en_EN
dc.rightshttp://creativecommons.org/licenses/by-nc-nd/4.0/deed.es-
dc.subjectHDACen_EN
dc.subjectCK2en_EN
dc.subjectMulti-target inhibitorsen_EN
dc.subjectDockingen_EN
dc.subjectMolecular dynamicsen_EN
dc.subjectCuAACen_EN
dc.subjectCytotoxic activityen_EN
dc.titleMultitarget Anticancer Agents Based on Histone Deacetylase and Protein Kinase CK2 Inhibitors.-
dc.typeArtículo-
dc.identifier.doihttps://doi:10.3390/molecules25071497-
dc.centroUniversidad San Pablo-CEU-
Aparece en las colecciones: Facultad de Farmacia




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