000130579 001__ 130579
000130579 005__ 20240126184245.0
000130579 0247_ $$2doi$$a10.1016/j.ejmech.2019.111661
000130579 0248_ $$2sideral$$a113507
000130579 037__ $$aART-2019-113507
000130579 041__ $$aeng
000130579 100__ $$aMármol, Inés$$uUniversidad de Zaragoza
000130579 245__ $$aAlkynyl Gold(I) complexes derived from 3-hydroxyflavones as multi-targeted drugs against colon cancer
000130579 260__ $$c2019
000130579 5060_ $$aAccess copy available to the general public$$fUnrestricted
000130579 5203_ $$aThe design of multi-targeted drugs has gained considerable interest in the last decade thanks to their advantages in the treatment of different diseases, including cancer. The simultaneous inhibition of selected targets from cancerous cells to induce their death represents an attractive objective for the medicinal chemist in order to enhance the efficiency of chemotherapy. In the present work, several alkynyl gold(I) phosphane complexes derived from 3-hydroxyflavones active against three human cancer cell lines, colorectal adenocarcinoma Caco-2/TC7, breast adenocarcinoma MCF-7 and hepatocellular carcinoma HepG2, have been synthesized and characterized. Moreover, these compounds display high selective index values towards differentiated Caco-2 cells, which are considered as a model of non-cancerous cells. The antiproliferative effect of the most active complexes [Au(L2b)PPh3] (3b) and [Au(L2c)PTA] (4c) on Caco-2 cells, seems to be mediated by the inhibition of the enzyme cyclooxygenase-1/2 and alteration of the activities of the redox enzymes thioredoxin reductase and glutathione reductase. Both complexes triggered cell death by apoptosis, alterations in cell cycle progression and increased of ROS production. These results provide support for the suggestion that multi-targeting approach involving the interaction with cyclooxygenase-1/2 and the redox enzymes that increases ROS production, enhances cell death in vitro. All these results indicate that complexes [Au(L2b)PPh3] and [Au(L2c)PTA] are promising antiproliferative agents for further anticancer drug development.
000130579 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B16-R17$$9info:eu-repo/grantAgreement/ES/DGA/E07-17R$$9info:eu-repo/grantAgreement/ES/ISCIII-CIBERObn/CB06-03-1012$$9info:eu-repo/grantAgreement/ES/MINECO/CTQ2016-75816-C2-1-P$$9info:eu-repo/grantAgreement/ES/MINECO/SAF2016-75441-R$$9info:eu-repo/grantAgreement/EUR/SUDOE/INTERREG/Redvalue-SOE1-PI-E0123
000130579 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
000130579 590__ $$a5.572$$b2019
000130579 591__ $$aCHEMISTRY, MEDICINAL$$b5 / 61 = 0.082$$c2019$$dQ1$$eT1
000130579 592__ $$a1.144$$b2019
000130579 593__ $$aDrug Discovery$$c2019$$dQ1
000130579 593__ $$aPharmacology$$c2019$$dQ1
000130579 593__ $$aOrganic Chemistry$$c2019$$dQ1
000130579 593__ $$aMedicine (miscellaneous)$$c2019$$dQ1
000130579 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000130579 700__ $$aCastellnou, Pilar
000130579 700__ $$aÁlvarez, Raquel
000130579 700__ $$0(orcid)0000-0003-0553-0695$$aGimeno, M. Concepción$$uUniversidad de Zaragoza
000130579 700__ $$0(orcid)0000-0002-3595-7668$$aRodríguez-Yoldi, M.Jesús$$uUniversidad de Zaragoza
000130579 700__ $$0(orcid)0000-0003-2457-3674$$aCerrada, Elena$$uUniversidad de Zaragoza
000130579 7102_ $$12010$$2760$$aUniversidad de Zaragoza$$bDpto. Química Inorgánica$$cÁrea Química Inorgánica
000130579 7102_ $$11005$$2410$$aUniversidad de Zaragoza$$bDpto. Farmacología y Fisiolog.$$cÁrea Fisiología
000130579 773__ $$g183 (2019), 111661 [14 pp.]$$pEur. j. med. chem.$$tEUROPEAN JOURNAL OF MEDICINAL CHEMISTRY$$x0223-5234
000130579 8564_ $$s1151090$$uhttps://zaguan.unizar.es/record/130579/files/texto_completo.pdf$$yPostprint
000130579 8564_ $$s1733583$$uhttps://zaguan.unizar.es/record/130579/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint
000130579 909CO $$ooai:zaguan.unizar.es:130579$$particulos$$pdriver
000130579 951__ $$a2024-01-26-18:11:25
000130579 980__ $$aARTICLE