86477 20210121114549.0 doi 10.1021/acs.jmedchem.5b00427 sideral 91427 ART-2015-91427 eng Frik, Malgorzata Cyclometalated Iminophosphorane Gold(III) and Platinum(II) Complexes. A Highly Permeable Cationic Platinum(II) Compound with Promising Anticancer Properties 2015 Access copy available to the general public Unrestricted New 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. info:eu-repo/grantAgreement/ES/MEC/FPU-AP2010-2372 info:eu-repo/grantAgreement/ES/MINECO/SAF2010-1490 info:eu-repo/semantics/openAccess by-nc http://creativecommons.org/licenses/by-nc/3.0/es/ 5.589 2015 CHEMISTRY, MEDICINAL 3 / 59 = 0.051 2015 Q1 T1 2.446 2015 Molecular Medicine 2015 Q1 Drug Discovery 2015 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Fernández-Gallardo, Jacob (orcid)0000-0002-7444-2341 Gonzalo, Óscar Universidad de Zaragoza Mangas-Sanjuan, Víctor González-Alvarez, Marta Serrano del Valle, Alfonso Universidad de Zaragoza Hu, Chunhua González-Alvarez, Isabel Bermejo, Marival (orcid)0000-0002-2315-9079 Marzo, Isabel Universidad de Zaragoza Contel, María 1002 050 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Biología Celular 58, 15 (2015), 5825-5841 J. med. chem. Journal of medicinal chemistry 0022-2623 3034640 http://zaguan.unizar.es/record/86477/files/texto_completo.pdf Versión publicada 128146 http://zaguan.unizar.es/record/86477/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:86477 articulos driver 2021-01-21-11:20:47 ARTICLE