Please use this identifier to cite or link to this item: http://hdl.handle.net/10637/13383

Multitarget Anticancer Agents Based on Histone Deacetylase and Protein Kinase CK2 Inhibitors.

Title: Multitarget Anticancer Agents Based on Histone Deacetylase and Protein Kinase CK2 Inhibitors.
Authors : Martínez, Regina
Di Geronimo Quintero, Bruno
Pastor, Myriam
Zapico Rodríguez, José María
Coderch Boué, Claire
Panchuk, Rostyslav
Skorokhyd, Nadia
Maslyk, Maciej
Ramos González, Ana
Pascual-Teresa Fernández, Beatriz de
Keywords: HDACCK2Multi-target inhibitorsDockingMolecular dynamicsCuAACCytotoxic activity
Abstract: The 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.
Description: Molecules, e-ISSN 1420-3049 , 2020, 25, 1497
URI: http://hdl.handle.net/10637/13383
Rights : http://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
Issue Date: 15-Feb-2020
Center : Universidad San Pablo-CEU
Appears in Collections:Facultad de Farmacia





Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.