78316 20200113145620.0 doi 10.1016/j.jinorgbio.2018.02.018 sideral 105291 ART-2018-105291 eng de la Cueva-Alique, I. Biological evaluation of water soluble arene Ru(II) enantiomers with amino-oxime ligands 2018 Access copy available to the general public Unrestricted New water soluble, enantiopure arene ruthenium compound SRuSN-(1R, 4S)-[(¿6-p-cymene)Ru{¿NH(Bn), ¿NOH}Cl]Cl (Bn = benzyl, 1a') has been synthesized. The novel compound along with that previously described RRuRN-(1S, 4R)-[(¿6-p-cymene)Ru{¿NH(Bn), ¿NOH}Cl]Cl (1a) was evaluated by polarimetry, ultra-violet and circular dichroism spectroscopy. The structure of novel ruthenium derivative 1a' was determined by single crystal X-ray crystallography. Both enantiomers have been tested against several cancer cell lines in vitro: prostate PC-3, lung A-549, pancreas MIA PaCa-2, colorectal HCT-116, leukemia Jurkat and cervical HeLa. Both enantiomers are active and versatile cytotoxic agents, showing IC50 values from 2 to 12 times lower than those found for cisplatin in the different cell lines evaluated. The mechanism of cell death induced by the metal compounds was analyzed in A-549 and Jurkat cell lines. Derivatives 1a and 1a' induced apoptotic cell death of A-549 cells while dose-dependent cell death mechanisms have been found in the Jurkat cell line. Compound-DNA interactions have been investigated by equilibrium dialysis, Fluorescence Resonance Energy Transfer (FRET) melting assays and viscometric titrations, revealing moderate binding affinity of 1a and 1a' towards duplex DNA. Finally, the efficacy of 1a in a preliminary in vivo assay of PC-3 xenografts in nude mice has been evaluated, resulting in a promising inhibition of tumor growth by 45%. Analysis of tumor tissue also showed a significant decrease of levels of crucial molecules in the invasive phenotype of PC-3 cells. info:eu-repo/grantAgreement/ES/MICINN/CTQ2014-58270-R info:eu-repo/semantics/openAccess by-nc-nd http://creativecommons.org/licenses/by-nc-nd/3.0/es/ 3.224 2018 CHEMISTRY, INORGANIC & NUCLEAR 11 / 45 = 0.244 2018 Q1 T1 BIOCHEMISTRY & MOLECULAR BIOLOGY 127 / 294 = 0.432 2018 Q2 T2 0.655 2018 Inorganic Chemistry 2018 Q2 Biochemistry 2018 Q2 info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion Sierra, S. Muñoz-Moreno, L. Pérez-Redondo, A. Bajo, A.M. (orcid)0000-0002-2315-9079 Marzo, I. Universidad de Zaragoza Gude, L. Cuenca, T. Royo, E. 1002 050 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Biología Celular 183 (2018), 32-42 J. inorg. biochem. JOURNAL OF INORGANIC BIOCHEMISTRY 0162-0134 1178293 http://zaguan.unizar.es/record/78316/files/texto_completo.pdf Postprint 54085 http://zaguan.unizar.es/record/78316/files/texto_completo.jpg?subformat=icon icon Postprint oai:zaguan.unizar.es:78316 articulos driver 2020-01-13-14:55:27 ARTICLE