000086477 001__ 86477
000086477 005__ 20210121114549.0
000086477 0247_ $$2doi$$a10.1021/acs.jmedchem.5b00427
000086477 0248_ $$2sideral$$a91427
000086477 037__ $$aART-2015-91427
000086477 041__ $$aeng
000086477 100__ $$aFrik, Malgorzata
000086477 245__ $$aCyclometalated Iminophosphorane Gold(III) and Platinum(II) Complexes. A Highly Permeable Cationic Platinum(II) Compound with Promising Anticancer Properties
000086477 260__ $$c2015
000086477 5060_ $$aAccess copy available to the general public$$fUnrestricted
000086477 5203_ $$aNew organometallic gold(III) and platinum(II) complexes containing iminophosphorane ligands are described. Most of them are more cytotoxic to a number of human cancer cell lines than cisplatin. Cationic Pt(II) derivatives 4 and 5, which differ only in the anion, Hg2Cl62– or PF6– respectively, display almost identical IC50 values in the sub-micromolar range (25–335-fold more active than cisplatin on these cell lines). The gold compounds induced mainly caspase-independent cell death, as previously reported for related cycloaurated compounds containing IM ligands. Cycloplatinated compounds 3, 4, and 5 can also activate alternative caspase-independent mechanisms of death. However, at short incubation times cell death seems to be mainly caspase dependent, suggesting that the main mechanism of cell death for these compounds is apoptosis. Mercury-free compound 5 does not interact with plasmid (pBR322) DNA or with calf thymus DNA. Permeability studies of 5 by two different assays, in vitro Caco-2 monolayers and a rat perfusion model, have revealed a high permeability profile for this compound (comparable to that of metoprolol or caffeine) and an estimated oral fraction absorbed of 100%, which potentially makes it a good candidate for oral administration.
000086477 536__ $$9info:eu-repo/grantAgreement/ES/MEC/FPU-AP2010-2372$$9info:eu-repo/grantAgreement/ES/MINECO/SAF2010-1490
000086477 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc$$uhttp://creativecommons.org/licenses/by-nc/3.0/es/
000086477 590__ $$a5.589$$b2015
000086477 591__ $$aCHEMISTRY, MEDICINAL$$b3 / 59 = 0.051$$c2015$$dQ1$$eT1
000086477 592__ $$a2.446$$b2015
000086477 593__ $$aMolecular Medicine$$c2015$$dQ1
000086477 593__ $$aDrug Discovery$$c2015$$dQ1
000086477 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000086477 700__ $$aFernández-Gallardo, Jacob
000086477 700__ $$0(orcid)0000-0002-7444-2341$$aGonzalo, Óscar$$uUniversidad de Zaragoza
000086477 700__ $$aMangas-Sanjuan, Víctor
000086477 700__ $$aGonzález-Alvarez, Marta
000086477 700__ $$aSerrano del Valle, Alfonso$$uUniversidad de Zaragoza
000086477 700__ $$aHu, Chunhua
000086477 700__ $$aGonzález-Alvarez, Isabel
000086477 700__ $$aBermejo, Marival
000086477 700__ $$0(orcid)0000-0002-2315-9079$$aMarzo, Isabel$$uUniversidad de Zaragoza
000086477 700__ $$aContel, María
000086477 7102_ $$11002$$2050$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Biología Celular
000086477 773__ $$g58, 15 (2015), 5825-5841$$pJ. med. chem.$$tJournal of medicinal chemistry$$x0022-2623
000086477 8564_ $$s3034640$$uhttps://zaguan.unizar.es/record/86477/files/texto_completo.pdf$$yVersión publicada
000086477 8564_ $$s128146$$uhttps://zaguan.unizar.es/record/86477/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000086477 909CO $$ooai:zaguan.unizar.es:86477$$particulos$$pdriver
000086477 951__ $$a2021-01-21-11:20:47
000086477 980__ $$aARTICLE