130579 20240126184245.0 doi 10.1016/j.ejmech.2019.111661 sideral 113507 ART-2019-113507 eng Mármol, Inés Universidad de Zaragoza Alkynyl Gold(I) complexes derived from 3-hydroxyflavones as multi-targeted drugs against colon cancer 2019 The design of multi-targeted drugs has gained considerable interest in the last decade thanks to their advantages in the treatment of different diseases, including cancer. The simultaneous inhibition of selected targets from cancerous cells to induce their death represents an attractive objective for the medicinal chemist in order to enhance the efficiency of chemotherapy. In the present work, several alkynyl gold(I) phosphane complexes derived from 3-hydroxyflavones active against three human cancer cell lines, colorectal adenocarcinoma Caco-2/TC7, breast adenocarcinoma MCF-7 and hepatocellular carcinoma HepG2, have been synthesized and characterized. Moreover, these compounds display high selective index values towards differentiated Caco-2 cells, which are considered as a model of non-cancerous cells. The antiproliferative effect of the most active complexes [Au(L2b)PPh3] (3b) and [Au(L2c)PTA] (4c) on Caco-2 cells, seems to be mediated by the inhibition of the enzyme cyclooxygenase-1/2 and alteration of the activities of the redox enzymes thioredoxin reductase and glutathione reductase. Both complexes triggered cell death by apoptosis, alterations in cell cycle progression and increased of ROS production. These results provide support for the suggestion that multi-targeting approach involving the interaction with cyclooxygenase-1/2 and the redox enzymes that increases ROS production, enhances cell death in vitro. All these results indicate that complexes [Au(L2b)PPh3] and [Au(L2c)PTA] are promising antiproliferative agents for further anticancer drug development. Access copy available to the general public Unrestricted info:eu-repo/grantAgreement/ES/DGA/B16-R17 info:eu-repo/grantAgreement/ES/DGA/E07-17R info:eu-repo/grantAgreement/ES/ISCIII-CIBERObn/CB06-03-1012 info:eu-repo/grantAgreement/ES/MINECO/CTQ2016-75816-C2-1-P info:eu-repo/grantAgreement/ES/MINECO/SAF2016-75441-R info:eu-repo/grantAgreement/EUR/SUDOE/INTERREG/Redvalue-SOE1-PI-E0123 info:eu-repo/semantics/openAccess by-nc-nd http://creativecommons.org/licenses/by-nc-nd/3.0/es/ 5.572 2019 CHEMISTRY, MEDICINAL 5 / 61 = 0.082 2019 Q1 T1 1.144 2019 Drug Discovery 2019 Q1 Pharmacology 2019 Q1 Organic Chemistry 2019 Q1 Medicine (miscellaneous) 2019 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion Castellnou, Pilar Álvarez, Raquel Gimeno, M. Concepción Universidad de Zaragoza (orcid)0000-0003-0553-0695 Rodríguez-Yoldi, M.Jesús Universidad de Zaragoza (orcid)0000-0002-3595-7668 Cerrada, Elena Universidad de Zaragoza (orcid)0000-0003-2457-3674 2010 760 Universidad de Zaragoza Dpto. Química Inorgánica Área Química Inorgánica 1005 410 Universidad de Zaragoza Dpto. Farmacología y Fisiolog. Área Fisiología 183 (2019), 111661 [14 pp.] Eur. j. med. chem. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 0223-5234 1151090 http://zaguan.unizar.es/record/130579/files/texto_completo.pdf Postprint 1733583 http://zaguan.unizar.es/record/130579/files/texto_completo.jpg?subformat=icon icon Postprint oai:zaguan.unizar.es:130579 articulos driver 2024-01-26-18:11:25 ARTICLE